id
stringlengths
7
8
tokens
sequence
ner_tags
sequence
texts
stringlengths
0
8.69k
input_ids
sequence
token_type_ids
sequence
attention_mask
sequence
labels
sequence
26925673
[ "The", "results", "of", "the", "present", "study", "revealed", "that", "EA", "exerts", "anti-proliferative", "and", "dose-dependent", "pro-apoptotic", "effects.", "Cytostatic", "and", "cytotoxic", "effects", "were", "also", "observed.", "p-Akt", "(at", "Thr308", " ", "and", "Ser473", ")", "was", "downregulated.", "Moreover,", "EA", "treatment", "was", "found", "to", "(i)", "reduce", "K-Ras", "protein", "expression;", "(ii)", "in", "cells", "transfected", "with", "siRNA", "and", "co-treated", "with", "EA,", "pronounced", "anti-proliferative", "effects", "as", "well", "as", "depletion", "of", "p-Akt", "(at", "Thr308)", "were", "detected." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 0, 0, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473 ) was downregulated. Moreover, EA treatment was found to (i) reduce K-Ras protein expression; (ii) in cells transfected with siRNA and co-treated with EA, pronounced anti-proliferative effects as well as depletion of p-Akt (at Thr308) were detected.
[ 2, 1920, 2274, 1927, 1920, 2481, 2161, 3404, 1988, 11377, 14235, 2246, 17, 9842, 1930, 3253, 17, 3100, 1965, 17, 6353, 2564, 18, 5521, 3857, 2002, 1930, 8377, 2564, 1985, 2222, 2528, 18, 58, 17, 5496, 12, 2019, 8481, 22661, 1930, 2375, 20939, 13, 1982, 9936, 18, 3950, 16, 11377, 2311, 1982, 2435, 1942, 12, 51, 13, 4412, 53, 17, 6520, 2213, 2294, 31, 12, 2890, 13, 1922, 2094, 5176, 1956, 5929, 1930, 2081, 17, 2868, 1956, 11377, 16, 9079, 2246, 17, 9842, 2564, 1966, 2486, 1966, 6882, 1927, 58, 17, 5496, 12, 2019, 8481, 22661, 13, 1985, 3330, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
26416897
[ "TBK1", "rs7486100", "was", "significantly", "associated", "with", "overall", "survival", "in", "95", "KRAS", "wild-type", "patients", "of", "TRIBE", "cohort", "in", "univariate", "analysis", "and", "had", "a", "strong", "trend", "in", "multivariable", "analysis;", "furthermore,", "the", "association", "of", "the", "T", "allele", "was", "observed", "for", "progression-free", "survival", "(PFS)", "in", "both", "univariate", "and", "multivariable", "analyses", "in", "FIRE3-bevacizumab", "but", "not", "cetuximab", "cohort.", "CCL2", "rs4586,", "CCL18", "rs14304,", "and", "IRF3", "rs2304205", " ", "had", "univariate", "and", "multivariable", "correlations", "with", "PFS", "in", "KRAS", "mutant", "patients", "of", "the", "TRIBE", "cohort,", "whereas", "they", "had", "no", "correlations", "in", "KRAS", "wild-type", "patients", "of", "the", "TRIBE", "cohort.", "No", "association", "was", "seen", "in", "control", "cohort." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 11, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS wild-type patients of the TRIBE cohort. No association was seen in control cohort.
[ 2, 28847, 26570, 28839, 9029, 1982, 2567, 2458, 1956, 3399, 3298, 1922, 3002, 11083, 3576, 17, 2601, 2132, 1927, 14521, 1021, 4382, 1922, 9895, 2333, 1930, 2430, 43, 3206, 5045, 1922, 11327, 2333, 31, 3677, 16, 1920, 3279, 1927, 1920, 62, 5465, 1982, 2528, 1958, 4380, 17, 3294, 3298, 12, 11133, 13, 1922, 2321, 9895, 1930, 11327, 3247, 1922, 11105, 1010, 17, 15250, 2308, 2084, 19418, 4382, 18, 18280, 4366, 6803, 11617, 16, 10322, 3928, 4366, 24428, 14743, 16, 1930, 23827, 4366, 4553, 14743, 23368, 2430, 9895, 1930, 11327, 6100, 1956, 11133, 1922, 11083, 3606, 2132, 1927, 1920, 14521, 1021, 4382, 16, 3417, 2611, 2430, 2239, 6100, 1922, 11083, 3576, 17, 2601, 2132, 1927, 1920, 14521, 1021, 4382, 18, 2239, 3279, 1982, 3945, 1922, 2285, 4382, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 11, 12, 12, 12, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
24435063
[ "This", "study", "explored", "the", "interest", "in", "genomic", "testing", "for", "modest", "changes", "in", "colorectal", "cancer", "risk", "and", "preferences", "for", "receiving", "genomic", "risk", "communications", "among", "individuals", "with", "intermediate", "disease", "risk", "due", "to", "a", "family", "history", "of", "colorectal", "cancer." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
This study explored the interest in genomic testing for modest changes in colorectal cancer risk and preferences for receiving genomic risk communications among individuals with intermediate disease risk due to a family history of colorectal cancer.
[ 2, 2052, 2161, 7255, 1920, 4501, 1922, 4935, 4213, 1958, 9194, 2840, 1922, 7820, 2539, 2565, 1930, 11127, 1958, 5962, 4935, 2565, 20518, 2706, 3445, 1956, 6129, 2573, 2565, 2810, 1942, 43, 3416, 4403, 1927, 7820, 2539, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
25421761
[ "[Application", "of", "molecular", "targeted", "agents", "in", "comprehensive", "treatment", "of", "gastrointestinal", "cancer]." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[Application of molecular targeted agents in comprehensive treatment of gastrointestinal cancer].
[ 2, 37, 4722, 1927, 3272, 5154, 4820, 1922, 6911, 2311, 1927, 8375, 2539, 39, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
1319833
[ "Loss", "of", "expression", "of", "the", "DCC", "gene", "during", "progression", "of", "colorectal", "carcinomas", "in", "familial", "adenomatous", "polyposis", "and", "non-familial", "adenomatous", "polyposis", "patients." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Loss of expression of the DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial adenomatous polyposis patients.
[ 2, 3257, 1927, 2294, 1927, 1920, 24649, 2359, 2409, 4380, 1927, 7820, 10691, 1922, 11444, 30390, 28641, 1930, 2447, 17, 11444, 30390, 28641, 2132, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
26925673
[ "Cellular", "genetic", "makeup", "(K-Ras-/p53-)", "was", "not", "likely", "to", "impose", "limitations", "on", "targeting", "EA", "in", "treatment", "of", "colon", "cancer.", "EA", "had", "a", "multi-disciplinary", "pro-apoptotic", "anti-proliferative", "approach,", "having", "inhibited", "Akt", "phosphorylation,", "induced", "cell", "cycle", "arrest", "and", "showed", "an", "anti-proliferative", "potential", "in", "HCT-116", "cells", "(expressing", "mutant", "K-Ras", "p53", "+)", "and", "Caco-2", "(K-Ras+/", "p53-),", "on", "response", "to", "potential", "anti-tumour", "effects", "of", "EA.", "In", "addition,", "the", "influence", "of", "K-Ras", "silencing", "in", "HCT-", "116", "cells", "was", "investigated." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Cellular genetic makeup (K-Ras-/p53-) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant K-Ras p53 +) and Caco-2 (K-Ras+/ p53-), on response to potential anti-tumour effects of EA. In addition, the influence of K-Ras silencing in HCT- 116 cells was investigated.
[ 2, 3689, 3299, 5144, 3481, 12, 53, 17, 6520, 17, 19, 5105, 17, 13, 1982, 2084, 3205, 1942, 26926, 5780, 1990, 5133, 11377, 1922, 2311, 1927, 4120, 2539, 18, 11377, 2430, 43, 2779, 17, 29811, 1965, 17, 6353, 2246, 17, 9842, 2998, 16, 4537, 5069, 5496, 4050, 16, 2719, 2024, 4048, 8048, 1930, 2594, 1925, 2246, 17, 9842, 2889, 1922, 10745, 17, 10922, 2094, 12, 4590, 3606, 53, 17, 6520, 5105, 15, 13, 1930, 19107, 17, 22, 12, 53, 17, 6520, 15, 19, 5105, 17, 13, 16, 1990, 2644, 1942, 2889, 2246, 17, 6383, 2564, 1927, 11377, 18, 1922, 2459, 16, 1920, 4039, 1927, 53, 17, 6520, 8343, 1922, 10745, 17, 10922, 2094, 1982, 3845, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
7557155
[ "The", "genetic", "basis", "of", "cancer", "involves", "certain", "classes", "of", "genes,", "particularly", "oncogenes,", "tumor-suppressor", "genes,", "and", "DNA", "mismatch", "repair", "genes.", "Originally", "identified", "in", "bacteria", "and", "yeast,", "the", "human", "homologues", "of", "DNA", "mismatch", "repair", "genes", "have", "been", "implicated", "in", "the", "pathogenesis", "of", "the", "hereditary", "nonpolyposis", "colorectal", "cancer", "syndromes,", "as", "well", "as", "a", "variety", "of", "different", "sporadic", "cancers.", "An", "appreciation", "of", "their", "role", "in", "cancer", "is", "predicated", "on", "an", "understanding", "of", "their", "function", "in", "the", "processes", "of", "DNA", "repair.", "This", "article", "reviews", "the", "recent", "developments", "and", "advances", "in", "the", "biology", "of", "the", "human", "DNA", "mismatch", "repair", "genes", "and", "their", "involvement", "in", "the", "pathogenesis", "of", "cancer." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The genetic basis of cancer involves certain classes of genes, particularly oncogenes, tumor-suppressor genes, and DNA mismatch repair genes. Originally identified in bacteria and yeast, the human homologues of DNA mismatch repair genes have been implicated in the pathogenesis of the hereditary nonpolyposis colorectal cancer syndromes, as well as a variety of different sporadic cancers. An appreciation of their role in cancer is predicated on an understanding of their function in the processes of DNA repair. This article reviews the recent developments and advances in the biology of the human DNA mismatch repair genes and their involvement in the pathogenesis of cancer.
[ 2, 1920, 3299, 4859, 1927, 2539, 7077, 4908, 7190, 1927, 2628, 16, 4443, 18582, 16, 2798, 17, 9241, 2628, 16, 1930, 2678, 10265, 5059, 2628, 18, 10398, 2899, 1922, 4802, 1930, 5688, 16, 1920, 2616, 18541, 1927, 2678, 10265, 5059, 2628, 2162, 2252, 6835, 1922, 1920, 6559, 1927, 1920, 16321, 24857, 26558, 2420, 1937, 7820, 2539, 12688, 16, 1966, 2486, 1966, 43, 5386, 1927, 2413, 13088, 5717, 18, 1925, 24030, 1927, 2310, 2770, 1922, 2539, 1977, 2771, 1981, 1990, 1925, 4339, 1927, 2310, 2347, 1922, 1920, 4028, 1927, 2678, 5059, 18, 2052, 5868, 8617, 1920, 3505, 15411, 1930, 9382, 1922, 1920, 7256, 1927, 1920, 2616, 2678, 10265, 5059, 2628, 1930, 2310, 5668, 1922, 1920, 6559, 1927, 2539, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9476377
[ "Familial", "adenomatous", "polyposis", "(FAP)", "is", "an", "autosomal", "dominant", "inherited", "disease", "characterized", "by", "multiple", "adenomatous", "polyps", "in", "the", "colon", "which", "progress", "to", "carcinoma.", "FAP", "is", "caused", "by", "germ-line", "mutation", "of", "the", "tumor-suppressor", "adenomatous", "polyposis", "coli", "(", "APC", "adenomatous", "polyposis", "coli", " ", "(APC)", "gene,", "the", "structure", "and", "coding", "sequence", "of", "which", "have", "been", "known", "from", "1991.", "The", "diagnosis", "of", "FAP", "has", "classically", "been", "based", "on", "the", "detection", "of", "multiple", "colorectal", "adenomas,", "often", "after", "carcinoma", "development.", "Presymptomatic", "genetic", "testing", "for", "the", "presence", "of", "an", "allele", "carrying", "the", "FAP", "mutation", "is", "now", "possible", "using", "a", "variety", "of", "techniques." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by multiple adenomatous polyps in the colon which progress to carcinoma. FAP is caused by germ-line mutation of the tumor-suppressor adenomatous polyposis coli ( APC adenomatous polyposis coli (APC) gene, the structure and coding sequence of which have been known from 1991. The diagnosis of FAP has classically been based on the detection of multiple colorectal adenomas, often after carcinoma development. Presymptomatic genetic testing for the presence of an allele carrying the FAP mutation is now possible using a variety of techniques.
[ 2, 11444, 30390, 28641, 12, 20592, 13, 1977, 1925, 13027, 6379, 12911, 2573, 4378, 2007, 3137, 30390, 17410, 1922, 1920, 4120, 2154, 4782, 1942, 5373, 18, 20592, 1977, 4189, 2007, 4363, 17, 2823, 3979, 1927, 1920, 2798, 17, 9241, 30390, 28641, 5178, 12, 9187, 30390, 28641, 5178, 12, 9187, 13, 2359, 16, 1920, 3170, 1930, 5804, 3244, 1927, 2154, 2162, 2252, 3171, 2037, 8802, 18, 1920, 3574, 1927, 20592, 2258, 24466, 2252, 2454, 1990, 1920, 3805, 1927, 3137, 7820, 16787, 16, 3868, 2256, 5373, 2740, 18, 2244, 2229, 9750, 3299, 4213, 1958, 1920, 2990, 1927, 1925, 5465, 8215, 1920, 20592, 3979, 1977, 5195, 3216, 2193, 43, 5386, 1927, 4941, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14734469
[ "The", "BRAF", "gene", "encodes", "a", "serine/threonine", "kinase", "and", "plays", "an", "important", "role", "in", "the", "mitogen-activated", "protein", "kinase", "signaling", "pathway.", "BRAF", "mutations", "in", "sporadic", "colorectal", "cancer", "with", "microsatellite", "instability", "(MSI)", "are", "more", "frequently", "detected", "than", "those", "in", "microsatellite", "stable", "cancer.", "In", "this", "study,", "we", "sought", "to", "compare", "the", "frequencies", "of", "BRAF", "mutations", "in", "sporadic", "colorectal", "cancer", "with", "MSI", "with", "those", "in", "hereditary", "nonpolyposis", "colorectal", "cancer", "(HNPCC)." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The BRAF gene encodes a serine/threonine kinase and plays an important role in the mitogen-activated protein kinase signaling pathway. BRAF mutations in sporadic colorectal cancer with microsatellite instability (MSI) are more frequently detected than those in microsatellite stable cancer. In this study, we sought to compare the frequencies of BRAF mutations in sporadic colorectal cancer with MSI with those in hereditary nonpolyposis colorectal cancer (HNPCC).
[ 2, 1920, 11346, 2359, 9937, 43, 8468, 19, 13143, 4016, 1930, 5705, 1925, 2715, 2770, 1922, 1920, 13584, 17, 4128, 2213, 4016, 3197, 3374, 18, 11346, 3527, 1922, 13088, 7820, 2539, 1956, 16069, 9557, 12, 17355, 13, 2032, 2253, 5467, 3330, 2254, 2690, 1922, 16069, 4700, 2539, 18, 1922, 2052, 2161, 16, 2038, 8758, 1942, 5175, 1920, 6458, 1927, 11346, 3527, 1922, 13088, 7820, 2539, 1956, 17355, 1956, 2690, 1922, 16321, 24857, 26558, 2420, 1937, 7820, 2539, 12, 9888, 7693, 1030, 13, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
15987719
[ "Inherited", "biallelic", "mutations", "in", "the", "human", "MUTYH", " ", "gene", "are", "responsible", "for", "the", "recessive", "syndrome--adenomatous", "colorectal", "polyposis", "(MUTYH", "associated", "polyposis,", "MAP)--which", "significantly", "increases", "the", "risk", "of", "colorectal", "cancer", "(CRC).", "Defective", "MUTYH", " ", "activity", "causes", "G:C", "to", "T:A", "transversions", "G:C", "to", "T:A", " ", "transversions", "in", "tumour", "APC", "and", "other", "genes", "thereby", "altering", "genomic", "integrity.", "We", "report", "that", "of", "the", "four", "established", "cell", "lines,", "derived", "from", "patients", "with", "the", "MAP", "phenotype", "and", "containing", "biallelic", "MUTYH", "mutations,", "three", "contain", "altered", "expressions", "of", "MUTYH", "protein", "(MUTYH", "Y165C(-/-),", "MUTYH", "1103delC/G382D", "and", "MUTYH", "Y165C/G382D", "but", "not", "MUTYH", "G382D(-/-)),", "but", "that", "all", "four", "cell", "lines", "have", "wild", "type", "levels", "of", "MUTYH", "mRNA.", "Mutant", "MUTYH", "proteins", "in", "these", "four", "cell", "lines", "possess", "significantly", "lowered", "binding", "and", "cleavage", "activities", "with", "heteroduplex", "oligonucleotides", "containing", "A.8-oxoG", "and", "8-oxoA.G", "mispairs.", "Transfection", "of", "mitochondrial", "or", "nuclear", "MUTYH", "cDNAs", "partially", "correct", "altered", "MUTYH", "expression", "and", "activity", "in", "these", "defective", "cell", "lines.", "Finally,", "we", "surprisingly", "find", "that", "defective", "MUTYH", "may", "not", "alter", "cell", "survival", "after", "hydrogen", "peroxide", "and", "menadione", "treatments.", "The", "Y165C", " ", "and", "1103delC", "biallelic", "mutations", " ", "in", "the", "human", "MUTYH", "gene", "are", "defective", "in", "DNA", "damage", "binding", "and", "repair." ]
[ 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 3, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 13, 0, 0, 13, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Inherited biallelic mutations in the human MUTYH gene are responsible for the recessive syndrome--adenomatous colorectal polyposis (MUTYH associated polyposis, MAP)--which significantly increases the risk of colorectal cancer (CRC). Defective MUTYH activity causes G:C to T:A transversions G:C to T:A transversions in tumour APC and other genes thereby altering genomic integrity. We report that of the four established cell lines, derived from patients with the MAP phenotype and containing biallelic MUTYH mutations, three contain altered expressions of MUTYH protein (MUTYH Y165C(-/-), MUTYH 1103delC/G382D and MUTYH Y165C/G382D but not MUTYH G382D(-/-)), but that all four cell lines have wild type levels of MUTYH mRNA. Mutant MUTYH proteins in these four cell lines possess significantly lowered binding and cleavage activities with heteroduplex oligonucleotides containing A.8-oxoG and 8-oxoA.G mispairs. Transfection of mitochondrial or nuclear MUTYH cDNAs partially correct altered MUTYH expression and activity in these defective cell lines. Finally, we surprisingly find that defective MUTYH may not alter cell survival after hydrogen peroxide and menadione treatments. The Y165C and 1103delC biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair.
[ 2, 12911, 27888, 1952, 3742, 3527, 1922, 1920, 2616, 2446, 1012, 1023, 2359, 2032, 5061, 1958, 1920, 13992, 4741, 17, 17, 30390, 7820, 28641, 12, 2446, 1012, 1023, 2458, 28641, 16, 4446, 13, 17, 17, 2154, 2567, 4041, 1920, 2565, 1927, 7820, 2539, 12, 8223, 13, 18, 9785, 2446, 1012, 1023, 2455, 5092, 49, 30, 45, 1942, 62, 30, 43, 22916, 2443, 49, 30, 45, 1942, 62, 30, 43, 22916, 2443, 1922, 6383, 9187, 1930, 2303, 2628, 6113, 12571, 4935, 7996, 18, 2038, 3809, 1988, 1927, 1920, 3006, 4379, 2024, 3557, 16, 3595, 2037, 2132, 1956, 1920, 4446, 4629, 1930, 3165, 27888, 1952, 3742, 2446, 1012, 1023, 3527, 16, 2559, 5531, 5520, 9678, 1927, 2446, 1012, 1023, 2213, 12, 2446, 1012, 1023, 25060, 5964, 1030, 12, 17, 19, 17, 13, 16, 2446, 1012, 1023, 8139, 19494, 1938, 1030, 19, 15991, 11715, 1007, 1930, 2446, 1012, 1023, 25060, 5964, 1030, 19, 15991, 11715, 1007, 2308, 2084, 2446, 1012, 1023, 15991, 11715, 1007, 12, 17, 19, 17, 13, 13, 16, 2308, 1988, 2136, 3006, 2024, 3557, 2162, 3576, 2601, 2428, 1927, 2446, 1012, 1023, 3616, 18, 3606, 2446, 1012, 1023, 2697, 1922, 2144, 3006, 2024, 3557, 7150, 2567, 13786, 2743, 1930, 6404, 4209, 1956, 11330, 3481, 2592, 12545, 3165, 43, 18, 28, 17, 18588, 1029, 1930, 28, 17, 18588, 1019, 18, 49, 5682, 4302, 21860, 18, 6496, 1927, 4596, 2014, 4254, 2446, 1012, 1023, 17072, 6426, 5550, 5520, 2446, 1012, 1023, 2294, 1930, 2455, 1922, 2144, 9785, 2024, 3557, 18, 4342, 16, 2038, 10091, 5387, 1988, 9785, 2446, 1012, 1023, 2278, 2084, 4238, 2024, 3298, 2256, 6201, 12316, 1930, 3925, 2713, 2290, 4930, 18, 1920, 25060, 5964, 1030, 1930, 8139, 19494, 1938, 1030, 27888, 1952, 3742, 3527, 1922, 1920, 2616, 2446, 1012, 1023, 2359, 2032, 9785, 1922, 2678, 4293, 2743, 1930, 5059, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 3, 4, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 13, 14, 14, 0, 13, 14, 14, 14, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
8709782
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
26416897
[ "##", "PATIENTS", "AND", "METHODS" ]
[ 0, 0, 0, 0 ]
## PATIENTS AND METHODS
[ 2, 7, 7, 2132, 1930, 2860, 3 ]
[ 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, -100 ]
9439149
[ "RER-positive", "phenotype", "occurs", "frequently", "in", "gastric", "carcinoma,", "although", "the", "frequency", "of", "RER-positive", "phenotype", "between", "young", "and", "elderly", "patient", "was", "not", "significantly", "different.", "Thus,", "the", "acquisition", "of", "RER-positive", "phenotype", "might", "be", "an", "early", "event", "in", "gastric", "carcinogenesis." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
RER-positive phenotype occurs frequently in gastric carcinoma, although the frequency of RER-positive phenotype between young and elderly patient was not significantly different. Thus, the acquisition of RER-positive phenotype might be an early event in gastric carcinogenesis.
[ 2, 21325, 17, 2843, 4629, 5110, 5467, 1922, 6319, 5373, 16, 2876, 1920, 3528, 1927, 21325, 17, 2843, 4629, 2192, 4201, 1930, 7354, 2774, 1982, 2084, 2567, 2413, 18, 2842, 16, 1920, 6165, 1927, 21325, 17, 2843, 4629, 3284, 1998, 1925, 3120, 4817, 1922, 6319, 12559, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
23132392
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
26925673
[ "##", "MATERIALS", "AND", "METHODS" ]
[ 0, 0, 0, 0 ]
## MATERIALS AND METHODS
[ 2, 7, 7, 4751, 1930, 2860, 3 ]
[ 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, -100 ]
26925673
[ "Cellular", "proliferation,", "morphology", "and", "cell", "cycle", "analysis", "were", "carried", "out", "in", "addition", "to", "Western", "blotting", "for", "detecting", "total", "Akt", "and", "p-Akt", "(at", "Thr308", "and", "Ser473)", "in", "the", "presence", "and", "absence", "of", "different", "concentrations", "of", "EA.", "Cell", "proliferation", "was", "also", "assessed", "in", "cells", "transfected", "with", "different", "concentrations", "of", "K-Ras", "siRNA", "or", "incubated", "with", "ellagic", "acid", "following", "transfection." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of K-Ras siRNA or incubated with ellagic acid following transfection.
[ 2, 3689, 4031, 16, 6076, 1930, 2024, 4048, 2333, 1985, 4371, 2397, 1922, 2459, 1942, 4540, 8390, 1958, 9227, 2698, 5496, 1930, 58, 17, 5496, 12, 2019, 8481, 22661, 1930, 2375, 20939, 13, 1922, 1920, 2990, 1930, 3905, 1927, 2413, 3295, 1927, 11377, 18, 2024, 4031, 1982, 2222, 3683, 1922, 2094, 5176, 1956, 2413, 3295, 1927, 53, 17, 6520, 5929, 2014, 3984, 1956, 20430, 12550, 2687, 2894, 6496, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
23497483
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
23132392
[ "##", "CONCLUSION" ]
[ 0, 0 ]
## CONCLUSION
[ 2, 7, 7, 4180, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
19276868
[ "An", "unbiased", "chemical", "screening", "using", "isogenic", "cell", "lines", "that", "only", "differ", "in", "the", "DPC4", " ", "gene", "was", "carried", "out", "to", "identify", "positive", "hits.", "Selected", "hits", "were", "further", "verified", "in", "additional", "isogenic", "cell", "lines", "and", "characterized", "in", "cancer", "cells", "using", "several", "different", "cellular", "assays." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
An unbiased chemical screening using isogenic cell lines that only differ in the DPC4 gene was carried out to identify positive hits. Selected hits were further verified in additional isogenic cell lines and characterized in cancer cells using several different cellular assays.
[ 2, 1925, 16584, 4399, 4449, 2193, 21703, 2024, 3557, 1988, 2444, 2129, 1922, 1920, 25488, 1006, 2359, 1982, 4371, 2397, 1942, 3512, 2843, 13560, 18, 3790, 13560, 1985, 2520, 8759, 1922, 3281, 21703, 2024, 3557, 1930, 4378, 1922, 2539, 2094, 2193, 2980, 2413, 3689, 4614, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14734469
[ "BRAF", "mutations", "are", "frequently", "present", "in", "sporadic", "colorectal", "cancer", "with", "methylated", "hMLH1,", "but", "not", "in", "HNPCC-related", "cancers.", "This", "discrepancy", "of", "BRAF", "mutations", "between", "sporadic", "MSI+", "cancer", "and", "HNPCC", "might", "be", "used", "in", "a", "strategy", "for", "the", "detection", "of", "HNPCC", "families." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
BRAF mutations are frequently present in sporadic colorectal cancer with methylated hMLH1, but not in HNPCC-related cancers. This discrepancy of BRAF mutations between sporadic MSI+ cancer and HNPCC might be used in a strategy for the detection of HNPCC families.
[ 2, 11346, 3527, 2032, 5467, 2481, 1922, 13088, 7820, 2539, 1956, 11882, 5833, 1024, 8600, 16, 2308, 2084, 1922, 9888, 7693, 1030, 17, 2712, 5717, 18, 2052, 12156, 1927, 11346, 3527, 2192, 13088, 17355, 15, 2539, 1930, 9888, 7693, 1030, 3284, 1998, 2251, 1922, 43, 4884, 1958, 1920, 3805, 1927, 9888, 7693, 1030, 5767, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
21261604
[ "Childhood", "brain", "tumours", "may", "be", "due", "to", "germline", "bi-allelic", "mismatch", "repair", "(MMR)", "gene", "mutations", "in", "MLH1,", "MSH2,", "MSH6", "or", "PMS2.", "These", "mutations", "can", "also", "lead", "to", "colorectal", "neoplasia", "and", "haematological", "malignancies.", "Here,", "we", "review", "this", "syndrome", "and", "present", "siblings", "with", "early-onset", "rectal", "adenoma", "and", "papillary", "glioneural", "brain", "tumour,", "respectively,", "due", "to", "novel", "germline", "bi-allelic", "PMS2", " ", "mutations", "mutations", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 3, 3, 0 ]
Childhood brain tumours may be due to germline bi-allelic mismatch repair (MMR) gene mutations in MLH1, MSH2, MSH6 or PMS2. These mutations can also lead to colorectal neoplasia and haematological malignancies. Here, we review this syndrome and present siblings with early-onset rectal adenoma and papillary glioneural brain tumour, respectively, due to novel germline bi-allelic PMS2 mutations mutations .
[ 2, 7238, 3068, 9313, 2278, 1998, 2810, 1942, 12237, 2273, 17, 13045, 10265, 5059, 12, 16744, 13, 2359, 3527, 1922, 25265, 16, 26693, 16, 19864, 1016, 2014, 13673, 1028, 18, 2144, 3527, 2112, 2222, 2949, 1942, 7820, 17773, 1930, 28691, 10672, 18, 3410, 16, 2038, 3043, 2052, 4741, 1930, 2481, 14715, 1956, 3120, 17, 4727, 11635, 16530, 1930, 15787, 6534, 2290, 2741, 3068, 6383, 16, 2763, 16, 2810, 1942, 4008, 12237, 2273, 17, 13045, 13673, 1028, 3527, 3527, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 3, 3, 0, -100 ]
9841584
[ "##", "SETTING" ]
[ 0, 0 ]
## SETTING
[ 2, 7, 7, 4308, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
25840688
[ "Genetic", "dissimilarity", "between", "primary", "colorectal", "carcinomas", "and", "their", "lymph", "node", "metastases:", "ploidy,", "p53,", "bcl-2,", "and", "c-myc", "expression--a", "pilot", "study." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.
[ 2, 3299, 26773, 2192, 3065, 7820, 10691, 1930, 2310, 3541, 6267, 8174, 30, 27860, 16, 5105, 16, 6717, 17, 22, 16, 1930, 45, 17, 5078, 2294, 17, 17, 43, 9404, 2161, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
12534642
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
12534642
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
6300869
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
12534642
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
22899730
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
20459617
[ "The", "total", "fraction", "of", "the", "genome", "with", "aberrant", "copy", "number", ",", "the", "overall", "genomic", "profile", "and", "the", "TP53", "mutation", "spectrum", "were", "similar", "between", "the", "two", "age", "groups.", "However,", "both", "the", "number", "of", "chromosomal", "aberrations", "and", "the", "number", "of", "breakpoints", "differed", "significantly", "between", "the", "groups.", "Gains", "of", "2q35,", "10q21.3-22.1", ",", "10q22.3", " ", "and", "19q13.2-13.31", " ", "and", "losses", "from", "1p31.3", ",", "1q21.1", ",", "2q21.2", ",", "4p16.1-q28.3,", "10p11.1", "and", "19p12,", "positions", "that", "in", "total", "contain", "more", "than", "500", "genes,", "were", "found", "significantly", "more", "often", "in", "the", "early", "onset", "group", "as", "compared", "to", "the", "late", "onset", "group.", "Integration", "analysis", "revealed", "a", "covariation", "of", "DNA", "copy", "number", "at", "these", "sites", "and", "mRNA", "expression", "for", "107", "of", "the", "genes.", "Seven", "of", "these", "genes,", "CLC,", "EIF4E,", "LTBP4,", "PLA2G12A,", "PPAT,", "RG9MTD2,", "and", "ZNF574", "10p11.1", "4p16.1-q28.3", ",", "10p11.1", "and", "19p12,", "positions", "that", "in", "total", "contain", "more", "than", "500", "genes,", "were", "found", "significantly", "more", "often", "in", "the", "early", "onset", "group", "as", "compared", "to", "the", "late", "onset", "group.", "Integration", "analysis", "revealed", "a", "covariation", "of", "DNA", "copy", "number", "at", "these", "sites", "and", "mRNA", "expression", "for", "107", "of", "the", "genes.", "Seven", "of", "these", "genes,", "CLC", ",", "EIF4E,", "LTBP4", "19p12", ",", "positions", "that", "in", "total", "contain", "more", "than", "500", "genes,", "were", "found", "significantly", "more", "often", "in", "the", "early", "onset", "group", "as", "compared", "to", "the", "late", "onset", "group.", "Integration", "analysis", "revealed", "a", "covariation", "of", "DNA", "copy", "number", "at", "these", "sites", "and", "mRNA", "expression", "for", "107", "of", "the", "genes.", "Seven", "of", "these", "genes,", "CLC,", "EIF4E,", "LTBP4,", "PLA2G12A,", "PPAT", "EIF4E", "TP53", " ", "mutation", "spectrum", "were", "similar", "between", "the", "two", "age", "groups.", "However,", "both", "the", "number", "of", "chromosomal", "aberrations", "and", "the", "number", "of", "breakpoints", "differed", "significantly", "between", "the", "groups.", "Gains", "of", "2q35,", "10q21.3-22.1,", "10q22.3", "and", "19q13.2-13.31", "and", "losses", "from", "1p31.3,", "1q21.1,", "2q21.2,", "4p16.1-q28.3,", "10p11.1", "and", "19p12,", "positions", "that", "in", "total", "contain", "more", "than", "500", "genes,", "were", "found", "significantly", "more", "often", "in", "the", "early", "onset", "group", "as", "compared", "to", "the", "late", "onset", "group.", "Integration", "analysis", "revealed", "a", "covariation", "of", "DNA", "copy", "number", "at", "these", "sites", "and", "mRNA", "expression", "for", "107", "of", "the", "genes.", "Seven", "of", "these", "genes,", "CLC,", "EIF4E,", "LTBP4,", "PLA2G12A", "2q35", ",", "10q21.3-22.1,", "10q22.3", "and", "19q13.2-13.31", "and", "losses", "from", "1p31.3,", "1q21.1,", "2q21.2,", "4p16.1-q28.3,", "10p11.1", "and", "19p12,", "positions", "that", "in", "total", "contain", "more", "than", "500", "genes,", "were", "found", "significantly", "more", "often", "in", "the", "early", "onset", "group", "as", "compared", "to", "the", "late", "onset", "group.", "Integration", "analysis", "revealed", "a", "covariation", "of", "DNA", "copy", "number", "at", "these", "sites", "and", "mRNA", "expression", "for", "107", "of", "the", "genes.", "Seven", "of", "these", "genes,", "CLC,", "EIF4E,", "LTBP4,", "PLA2G12A,", "PPAT,", "RG9MTD2", "losses", " ", "from", "1p31.3,", "1q21.1,", "2q21.2,", "4p16.1-q28.3,", "10p11.1", "and", "19p12,", "positions", "that", "in", "total", "contain", "more", "than", "500", "genes,", "were", "found", "significantly", "more", "often", "in", "the", "early", "onset", "group", "as", "compared", "to", "the", "late", "onset", "group.", "Integration", "analysis", "revealed", "a", "covariation", "of", "DNA", "copy", "number", "at", "these", "sites", "and", "mRNA", "expression", "for", "107", "of", "the", "genes.", "Seven", "of", "these", "genes,", "CLC,", "EIF4E,", "LTBP4,", "PLA2G12A,", "PPAT,", "RG9MTD2,", "and", "ZNF574,", "had", "significantly", "different", "mRNA", "expression", "comparing", "median", "expression", "levels", "across", "the", "transcriptome", "between", "the", "two", "groups." ]
[ 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 0, 7, 0, 0, 7, 0, 0, 0, 0, 7, 0, 7, 0, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 7, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 1, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The total fraction of the genome with aberrant copy number , the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1 , 10q22.3 and 19q13.2-13.31 and losses from 1p31.3 , 1q21.1 , 2q21.2 , 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574 10p11.1 4p16.1-q28.3 , 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC , EIF4E, LTBP4 19p12 , positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT EIF4E TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A 2q35 , 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2 losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups.
[ 2, 1920, 2698, 3906, 1927, 1920, 3843, 1956, 9801, 6983, 2529, 16, 1920, 3399, 4935, 5174, 1930, 1920, 13544, 3979, 5648, 1985, 2551, 2192, 1920, 2288, 2632, 2671, 18, 2406, 16, 2321, 1920, 2529, 1927, 9220, 16303, 1930, 1920, 2529, 1927, 23800, 8459, 2567, 2192, 1920, 2671, 18, 13241, 1927, 22, 1055, 5798, 16, 2119, 23470, 1009, 18, 23, 17, 2950, 18, 21, 16, 2119, 23470, 1028, 18, 23, 1930, 2282, 16886, 1010, 18, 22, 17, 2590, 18, 3470, 1930, 11783, 2037, 21727, 6800, 18, 23, 16, 28798, 4716, 18, 21, 16, 22, 23470, 1009, 18, 22, 16, 24, 5113, 1016, 18, 21, 17, 22808, 1025, 18, 23, 16, 2119, 5113, 1009, 18, 21, 1930, 2282, 5113, 1028, 16, 6490, 1988, 1922, 2698, 5531, 2253, 2254, 4599, 2628, 16, 1985, 2435, 2567, 2253, 3868, 1922, 1920, 3120, 4727, 2210, 1966, 2452, 1942, 1920, 5058, 4727, 2210, 18, 7122, 2333, 3404, 43, 7552, 1943, 1927, 2678, 6983, 2529, 2019, 2144, 3402, 1930, 3616, 2294, 1958, 9176, 1927, 1920, 2628, 18, 5260, 1927, 2144, 2628, 16, 21234, 16, 20798, 16, 3457, 3846, 1006, 16, 21334, 9114, 5896, 16, 27301, 1031, 16, 9372, 1026, 8625, 9091, 16, 1930, 20844, 5071, 1006, 2119, 5113, 1009, 18, 21, 24, 5113, 1016, 18, 21, 17, 22808, 1025, 18, 23, 16, 2119, 5113, 1009, 18, 21, 1930, 2282, 5113, 1028, 16, 6490, 1988, 1922, 2698, 5531, 2253, 2254, 4599, 2628, 16, 1985, 2435, 2567, 2253, 3868, 1922, 1920, 3120, 4727, 2210, 1966, 2452, 1942, 1920, 5058, 4727, 2210, 18, 7122, 2333, 3404, 43, 7552, 1943, 1927, 2678, 6983, 2529, 2019, 2144, 3402, 1930, 3616, 2294, 1958, 9176, 1927, 1920, 2628, 18, 5260, 1927, 2144, 2628, 16, 21234, 16, 20798, 16, 3457, 3846, 1006, 2282, 5113, 1028, 16, 6490, 1988, 1922, 2698, 5531, 2253, 2254, 4599, 2628, 16, 1985, 2435, 2567, 2253, 3868, 1922, 1920, 3120, 4727, 2210, 1966, 2452, 1942, 1920, 5058, 4727, 2210, 18, 7122, 2333, 3404, 43, 7552, 1943, 1927, 2678, 6983, 2529, 2019, 2144, 3402, 1930, 3616, 2294, 1958, 9176, 1927, 1920, 2628, 18, 5260, 1927, 2144, 2628, 16, 21234, 16, 20798, 16, 3457, 3846, 1006, 16, 21334, 9114, 5896, 16, 27301, 1031, 20798, 13544, 3979, 5648, 1985, 2551, 2192, 1920, 2288, 2632, 2671, 18, 2406, 16, 2321, 1920, 2529, 1927, 9220, 16303, 1930, 1920, 2529, 1927, 23800, 8459, 2567, 2192, 1920, 2671, 18, 13241, 1927, 22, 1055, 5798, 16, 2119, 23470, 1009, 18, 23, 17, 2950, 18, 21, 16, 2119, 23470, 1028, 18, 23, 1930, 2282, 16886, 1010, 18, 22, 17, 2590, 18, 3470, 1930, 11783, 2037, 21727, 6800, 18, 23, 16, 28798, 4716, 18, 21, 16, 22, 23470, 1009, 18, 22, 16, 24, 5113, 1016, 18, 21, 17, 22808, 1025, 18, 23, 16, 2119, 5113, 1009, 18, 21, 1930, 2282, 5113, 1028, 16, 6490, 1988, 1922, 2698, 5531, 2253, 2254, 4599, 2628, 16, 1985, 2435, 2567, 2253, 3868, 1922, 1920, 3120, 4727, 2210, 1966, 2452, 1942, 1920, 5058, 4727, 2210, 18, 7122, 2333, 3404, 43, 7552, 1943, 1927, 2678, 6983, 2529, 2019, 2144, 3402, 1930, 3616, 2294, 1958, 9176, 1927, 1920, 2628, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 8, 8, 8, 8, 8, 0, 7, 8, 8, 8, 8, 0, 7, 8, 8, 8, 8, 8, 8, 8, 8, 0, 0, 0, 7, 8, 8, 8, 0, 7, 8, 8, 8, 0, 7, 8, 8, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 7, 8, 8, 8, 8, 7, 8, 8, 8, 8, 8, 8, 8, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 1, 2, 2, 7, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
17350669
[ "Overexpression", "of", "fatty", "acid", "synthase", "(FASN),", "a", "key", "enzyme", "for", "de", "novo", "lipogenesis,", "is", "observed", "in", "many", "cancers", "including", "colorectal", "cancer", "and", "is", "associated", "with", "poor", "clinical", "outcomes.", "Cellular", "FASN", "FASN", "),", "a", "key", "enzyme", "for", "de", "novo", "lipogenesis,", "is", "observed", "in", "many", "cancers", "including", "colorectal", "cancer", "and", "is", "associated", "with", "poor", "clinical", "outcomes.", "Cellular", "FASN", "expression", "is", "physiologically", "upregulated", "in", "a", "state", "of", "energy", "excess.", "Obesity", "and", "excess", "energy", "balance", "have", "been", "known", "to", "be", "risk", "factors", "for", "colorectal", "cancer.", "High", "degree", "of", "microsatellite", "instability", "(MSI-H)", "is", "a", "distinct", "phenotype", "in", "colorectal", "cancer,", "associated", "with", "CpG", "island", "methylator", "phenotype", "(CIMP).", "Previous", "data", "suggest", "that", "obesity", "or", "altered", "energy", "balance", "may", "potentially", "modify", "risks", "for", "MSI-H", "cancers", "and", "microsatellite", "stable", "(MSS)", "cancers", "differently.", "However,", "the", "relationship", "between", "MSI", "and", "FASN", "overexpression", "has", "not", "been", "investigated.", "Using", "976", "cases", "of", "population-based", "colorectal", "cancer", "samples", "from", "2", "large", "prospective", "cohort", "studies,", "we", "correlated", "FASN", "expression", "(by", "immunohistochemistry)", "with", "MSI,", "KRAS", "and", "BRAF", "mutations,", "p53", "expression", "(by", "immunohistochemistry),", "and", "CIMP", "status", "[determined", "by", "MethyLight", "for", "8", "CIMP-specific", "gene", "promoters", "including", "CACNA1G,", "CDKN2A", "(p16),", "CRABP1,", "IGF2,", "MLH1,", "NEUROG1,", "RUNX3,", "and", "SOCS1].", "Marked", "(2+)", "FASN", "overexpression", "was", "observed", "in", "110", "(11%)", "of", "the", "976", "tumors", "and", "was", "significantly", "more", "common", "in", "MSI-H", "tumors", "(21%", "[28/135])", "than", "MSI-low", "(5.6%", "[4/72],", "P", "=", ".004)", "and", "MSS", "tumors", "(11%", "[72/678],", "P", "=", ".001).", "The", "association", "between", "FASN", "microsatellite", "instability", " ", "(MSI-H)", "is", "a", "distinct", "phenotype", "in", "colorectal", "cancer,", "associated", "with", "CpG", "island", "methylator", "phenotype", "(CIMP).", "Previous", "data", "suggest", "that", "obesity", "or", "altered", "energy", "balance", "may", "potentially", "modify", "risks", "for", "MSI-H", "cancers", "and", "microsatellite", "stable", "(MSS)", "cancers", "differently.", "However,", "the", "relationship", "between", "MSI", "and", "FASN", "overexpression", "has", "not", "been", "investigated.", "Using", "976", "cases", "of", "population-based", "colorectal", "cancer", "samples", "from", "2", "large", "prospective", "cohort", "studies,", "we", "correlated", "FASN", "expression", "(by", "immunohistochemistry)", "with", "MSI,", "KRAS", "and", "BRAF", "mutations,", "p53", "expression", "(by", "immunohistochemistry),", "and", "CIMP", "status", "[determined", "by", "MethyLight", "for", "8", "CIMP-specific", "gene", "promoters", "including", "CACNA1G,", "CDKN2A", "(p16),", "CRABP1,", "IGF2,", "MLH1,", "NEUROG1,", "RUNX3,", "and", "SOCS1].", "Marked", "(2+)", "FASN", "overexpression", "was", "observed", "in", "110", "(11%)", "of", "the", "976", "tumors", "and", "was", "significantly", "more", "common", "in", "MSI-H", "tumors", "(21%", "[28/135])", "than", "MSI-low", "(5.6%", "[4/72],", "P", "=", ".004)", "and", "MSS", "tumors", "(11%", "[72/678],", "P", "=", ".001).", "The", "association", "between", "FASN", "overexpression", "and", "MSI-H", "persisted", "even", "after", "stratification", "by", "CIMP", "status.", "In", "contrast,", "FASN", " ", "overexpression", "was", "not", "correlated", "with", "CIMP", "after", "stratification", "by", "MSI", "status.", "Fatty", "acid", "synthase", "overexpression", "was", "not", "significantly", "correlated", "with", "sex,", "tumor", "location,", "p53,", "or", "KRAS/BRAF", "status.", "In", "conclusion,", "FASN", "overexpression", "in", "colorectal", "cancer", "is", "associated", "with", "MSI-H,", "independent", "of", "CIMP", "status." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Overexpression of fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is observed in many cancers including colorectal cancer and is associated with poor clinical outcomes. Cellular FASN FASN ), a key enzyme for de novo lipogenesis, is observed in many cancers including colorectal cancer and is associated with poor clinical outcomes. Cellular FASN expression is physiologically upregulated in a state of energy excess. Obesity and excess energy balance have been known to be risk factors for colorectal cancer. High degree of microsatellite instability (MSI-H) is a distinct phenotype in colorectal cancer, associated with CpG island methylator phenotype (CIMP). Previous data suggest that obesity or altered energy balance may potentially modify risks for MSI-H cancers and microsatellite stable (MSS) cancers differently. However, the relationship between MSI and FASN overexpression has not been investigated. Using 976 cases of population-based colorectal cancer samples from 2 large prospective cohort studies, we correlated FASN expression (by immunohistochemistry) with MSI, KRAS and BRAF mutations, p53 expression (by immunohistochemistry), and CIMP status [determined by MethyLight for 8 CIMP-specific gene promoters including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1]. Marked (2+) FASN overexpression was observed in 110 (11%) of the 976 tumors and was significantly more common in MSI-H tumors (21% [28/135]) than MSI-low (5.6% [4/72], P = .004) and MSS tumors (11% [72/678], P = .001). The association between FASN microsatellite instability (MSI-H) is a distinct phenotype in colorectal cancer, associated with CpG island methylator phenotype (CIMP). Previous data suggest that obesity or altered energy balance may potentially modify risks for MSI-H cancers and microsatellite stable (MSS) cancers differently. However, the relationship between MSI and FASN overexpression has not been investigated. Using 976 cases of population-based colorectal cancer samples from 2 large prospective cohort studies, we correlated FASN expression (by immunohistochemistry) with MSI, KRAS and BRAF mutations, p53 expression (by immunohistochemistry), and CIMP status [determined by MethyLight for 8 CIMP-specific gene promoters including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1]. Marked (2+) FASN overexpression was observed in 110 (11%) of the 976 tumors and was significantly more common in MSI-H tumors (21% [28/135]) than MSI-low (5.6% [4/72], P = .004) and MSS tumors (11% [72/678], P = .001). The association between FASN overexpression and MSI-H persisted even after stratification by CIMP status. In contrast, FASN overexpression was not correlated with CIMP after stratification by MSI status. Fatty acid synthase overexpression was not significantly correlated with sex, tumor location, p53, or KRAS/BRAF status. In conclusion, FASN overexpression in colorectal cancer is associated with MSI-H, independent of CIMP status.
[ 2, 5616, 1927, 5934, 2687, 8921, 12, 4557, 1022, 13, 16, 43, 3834, 4113, 1958, 2028, 9441, 27113, 16, 1977, 2528, 1922, 3086, 5717, 2710, 7820, 2539, 1930, 1977, 2458, 1956, 3930, 2535, 3685, 18, 3689, 4557, 1022, 4557, 1022, 13, 16, 43, 3834, 4113, 1958, 2028, 9441, 27113, 16, 1977, 2528, 1922, 3086, 5717, 2710, 7820, 2539, 1930, 1977, 2458, 1956, 3930, 2535, 3685, 18, 3689, 4557, 1022, 2294, 1977, 15899, 7675, 1922, 43, 3360, 1927, 3844, 5799, 18, 5379, 1930, 5799, 3844, 6766, 2162, 2252, 3171, 1942, 1998, 2565, 2790, 1958, 7820, 2539, 18, 2149, 4647, 1927, 16069, 9557, 12, 17355, 17, 50, 13, 1977, 43, 4493, 4629, 1922, 7820, 2539, 16, 2458, 1956, 9383, 10269, 4963, 3061, 4629, 12, 20090, 1034, 13, 18, 2555, 2230, 3220, 1988, 5379, 2014, 5520, 3844, 6766, 2278, 5063, 11675, 7481, 1958, 17355, 17, 50, 5717, 1930, 16069, 4700, 12, 25826, 13, 5717, 11874, 18, 2406, 16, 1920, 3303, 2192, 17355, 1930, 4557, 1022, 5616, 2258, 2084, 2252, 3845, 18, 2193, 5749, 1016, 2919, 1927, 2973, 17, 2454, 7820, 2539, 2785, 2037, 22, 3103, 6315, 4382, 2351, 16, 2038, 4374, 4557, 1022, 2294, 12, 2007, 9101, 13, 1956, 17355, 16, 11083, 1930, 11346, 3527, 16, 5105, 2294, 12, 2007, 9101, 13, 16, 1930, 20090, 1034, 3642, 37, 3180, 2007, 4963, 2227, 1958, 28, 20090, 1034, 17, 2487, 2359, 9026, 2710, 9703, 2175, 1009, 1029, 16, 26969, 12, 14120, 13, 16, 25493, 5113, 16, 25102, 16, 25265, 16, 3366, 9114, 16, 4747, 12001, 16, 1930, 28317, 1009, 39, 18, 4961, 12, 22, 15, 13, 4557, 1022, 5616, 1982, 2528, 1922, 8139, 12, 2513, 9, 13, 1927, 1920, 5749, 1016, 3861, 1930, 1982, 2567, 2253, 3059, 1922, 17355, 17, 50, 3861, 12, 2900, 9, 37, 3158, 19, 11477, 39, 13, 2254, 17355, 17, 2330, 12, 25, 18, 26, 9, 37, 24, 19, 4395, 39, 16, 58, 33, 18, 11373, 13, 1930, 25826, 3861, 12, 2513, 9, 37, 4395, 19, 4838, 1025, 39, 16, 58, 33, 18, 3472, 13, 18, 1920, 3279, 2192, 4557, 1022, 16069, 9557, 12, 17355, 17, 50, 13, 1977, 43, 4493, 4629, 1922, 7820, 2539, 16, 2458, 1956, 9383, 10269, 4963, 3061, 4629, 12, 20090, 1034, 13, 18, 2555, 2230, 3220, 1988, 5379, 2014, 5520, 3844, 6766, 2278, 5063, 11675, 7481, 1958, 17355, 17, 50, 5717, 1930, 16069, 4700, 12, 25826, 13, 5717, 11874, 18, 2406, 16, 1920, 3303, 2192, 17355, 1930, 4557, 1022, 5616, 2258, 2084, 2252, 3845, 18, 2193, 5749, 1016, 2919, 1927, 2973, 17, 2454, 7820, 2539, 2785, 2037, 22, 3103, 6315, 4382, 2351, 16, 2038, 4374, 4557, 1022, 2294, 12, 2007, 9101, 13, 1956, 17355, 16, 11083, 1930, 11346, 3527, 16, 5105, 2294, 12, 2007, 9101, 13, 16, 1930, 20090, 1034, 3642, 37, 3180, 2007, 4963, 2227, 1958, 28, 20090, 1034, 17, 2487, 2359, 9026, 2710, 9703, 2175, 1009, 1029, 16, 26969, 12, 14120, 13, 16, 25493, 5113, 16, 25102, 16, 25265, 16, 3366, 9114, 16, 4747, 12001, 16, 1930, 28317, 1009, 39, 18, 4961, 12, 22, 15, 13, 4557, 1022, 5616, 1982, 2528, 1922, 8139, 12, 2513, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14645426
[ "In", "five", "of", "22", "patients", "with", "a", "positive", "first-degree", "family", "history", "for", "hereditary", "nonpolyposis", "colorectal", "cancer", "(HNPCC)-related", "cancers,", "pathogenic", "germline", "mutations", "were", "found", "(one", "MLH1,", "three", "MSH2,", "and", "one", "MSH6).", "Four", "mutation", "carriers", "belonged", "to", "families", "fulfilling", "the", "revised", "Amsterdam", "criteria.", "No", "mutations", "were", "found", "in", "the", "35", "patients", "without", "such", "family", "history", "(P", "=.006).", "MSI", "was", "detected", "in", "20", "of", "57", "cancers,", "among", "which", "four", "were", "from", "mutation", "MSI", " ", "analysis,", "five", "consensus", "markers", "were", "used,", "and", "immunostaining", "of", "the", "three", "MMR", "proteins", "was", "performed." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
In five of 22 patients with a positive first-degree family history for hereditary nonpolyposis colorectal cancer (HNPCC)-related cancers, pathogenic germline mutations were found (one MLH1, three MSH2, and one MSH6). Four mutation carriers belonged to families fulfilling the revised Amsterdam criteria. No mutations were found in the 35 patients without such family history (P =.006). MSI was detected in 20 of 57 cancers, among which four were from mutation MSI analysis, five consensus markers were used, and immunostaining of the three MMR proteins was performed.
[ 2, 1922, 3628, 1927, 2950, 2132, 1956, 43, 2843, 2561, 17, 4647, 3416, 4403, 1958, 16321, 24857, 26558, 2420, 1937, 7820, 2539, 12, 9888, 7693, 1030, 13, 17, 2712, 5717, 16, 8070, 12237, 3527, 1985, 2435, 12, 2340, 25265, 16, 2559, 26693, 16, 1930, 2340, 19864, 1016, 13, 18, 3006, 3979, 8974, 18293, 1942, 5767, 28606, 1920, 10041, 27002, 4164, 18, 2239, 3527, 1985, 2435, 1922, 1920, 3259, 2132, 2979, 2427, 3416, 4403, 12, 58, 33, 18, 12791, 13, 18, 17355, 1982, 3330, 1922, 2036, 1927, 4786, 5717, 16, 2706, 2154, 3006, 1985, 2037, 3979, 17355, 2333, 16, 3628, 7076, 4432, 1985, 2251, 16, 1930, 10930, 1927, 1920, 2559, 16744, 2697, 1982, 2593, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
22396040
[ "The", "associations", "between", "four", "common", "genetic", "polymorphisms", "of", "transforming", "growth", "factor-β1", "(", "TGF-β1", " ", "-509", "C", ">", "T,", "+869", "T", ">", "C,", "+915", "G", ">", "C,", "and", "-800", "G", ">", "A)", "and", "risk", "of", "colorectal", "tumor", "(including", "adenoma", "and", "cancer)", "have", "been", "widely", "studied.", "To", "date,", "no", "conclusions", "could", "be", "available", "because", "of", "controversial", "results", "reported.", "Thus,", "we", "conducted", "a", "meta-analysis", "to", "further", "assess", "the", "associations.", "We", "searched", "the", "databases", "of", "Medline,", "Embase,", "and", "Wangfang", "to", "identify", "eligible", "studies,", "and", "latest", "update", "was", "on", "January", "1,", "2012.", "Odds", "ratio", "(OR)", "and", "95%", "confidence", "interval", "(95%CI)", "were", "calculated", "to", "present", "the", "associations.", "Our", "meta-analysis", "indicated", "that", "TGF-β1", "-509", "C", ">", "T,", "+869", "T", ">", "C,", "+915", "G", ">", "C,", "and", "-800", "G", ">", "A", "were", "not", "associated", "with", "risk", "of", "colorectal", "adenoma", "(OR", "=", "0.89", "for", "C", "carriers", "vs.", "TT", "for", "-509", "C", ">", "T,", "1.03", "for", "C", "carriers", "vs.", "TT", "for", "+869", "T", ">", "C,", "1.09", "for", "C", "carriers", "vs.", "GG", "for", "+915", "G", ">", "C", "-509", "C", ">", "T", ",", "+869", "T", ">", "C", ",", "+915", "G", ">", "C,", "and", "-800", "G", ">", "A)", "and", "risk", "of", "colorectal", "tumor", "(including", "adenoma", "and", "cancer)", "have", "been", "widely", "studied.", "To", "date,", "no", "conclusions", "could", "be", "available", "because", "of", "controversial", "results", "reported.", "Thus,", "we", "conducted", "a", "meta-analysis", "to", "further", "assess", "the", "associations.", "We", "searched", "the", "databases", "of", "Medline,", "Embase,", "and", "Wangfang", "to", "identify", "eligible", "studies,", "and", "latest", "update", "was", "on", "January", "1,", "2012.", "Odds", "ratio", "(OR)", "and", "95%", "confidence", "interval", "(95%CI)", "were", "calculated", "to", "present", "the", "associations.", "Our", "meta-analysis", "indicated", "that", "TGF-β1", "-800", "G", ">", "A", ")", "and", "risk", "of", "colorectal", "tumor", "(including", "adenoma", "and", "cancer)", "have", "been", "widely", "studied.", "To", "date,", "no", "conclusions", "could", "be", "available", "because", "of", "controversial", "results", "reported.", "Thus,", "we", "conducted", "a", "meta-analysis", "to", "further", "assess", "the", "associations.", "We", "searched", "the", "databases", "of", "Medline,", "Embase,", "and", "Wangfang", "to", "identify", "eligible", "studies,", "and", "latest", "update", "was", "on", "January", "1,", "2012.", "Odds", "ratio", "(OR)", "and", "95%", "confidence", "interval", "(95%CI)", "were", "calculated", "to", "present", "the", "associations.", "Our", "meta-analysis", "indicated", "that", "TGF-β1", "-509", "C", ">", "T,", "+869", "T", ">", "C", "-509", "C", ">", "T", ",", "+869", "T", ">", "C,", "+915", "G", ">", "C", ",", "and", "-800", "G", ">", "A", " ", "were", "not", "associated", "with", "risk", "of", "colorectal", "adenoma", "(OR", "=", "0.89", "for", "C", "carriers", "vs.", "TT", "for", "-509", "C", ">", "T,", "1.03", "for", "C", "carriers", "vs.", "TT", "for", "+869", "T", ">", "C", "+915", "G", ">", "C", ",", "and", "-800", "G", ">", "A)", "and", "risk", "of", "colorectal", "tumor", "(including", "adenoma", "and", "cancer)", "have", "been", "widely", "studied.", "To", "date,", "no", "conclusions", "could", "be", "available", "because", "of", "controversial", "results", "reported.", "Thus,", "we", "conducted", "a", "meta-analysis", "to", "further", "assess", "the", "associations.", "We", "searched", "the", "databases", "of", "Medline,", "Embase,", "and", "Wangfang", "to", "identify", "eligible", "studies,", "and", "latest", "update", "was", "on", "January", "1,", "2012.", "Odds", "ratio", "(OR)", "and", "95%", "confidence", "interval", "(95%CI)", "were", "calculated", "to", "present", "the", "associations.", "Our", "meta-analysis", "indicated", "that", "TGF-β1", "-509", "C", ">", "T,", "+869", "T", ">", "C,", "+915", "G", ">", "C,", "and", "-800", "G", ">", "A", "were", "not", "associated", "with", "risk", "of", "colorectal", "adenoma", "(OR", "=", "0.89", "for", "C", "carriers", "vs.", "TT", "for", "-509", "C", ">", "T,", "1.03", "for", "C", "carriers", "vs.", "TT", "for", "+869", "T", ">", "C,", "1.09", "for", "C", "carriers", "vs.", "GG", "for", "+915", "G", ">", "C,", "and", "1.19", "for", "A", "carriers", "vs.", "GG", "for", "800", "G", ">", "A).", "However,", "C", "allele", "of", "TGF-β1", "-509", "C", ">", "T", "and", "A", "allele", "of", "-800", "G", ">", "A", "were", "associated", "with", "increased", "risk", "of", "colorectal", "cancer", "(CRC),", "and", "OR", "(95%CI)", "was", "1.23", "(0.99-1.52)", "for", "CC", "vs.", "TT", "for", "-509", "C", ">", "T", "and", "6.64", "(3.46-12.72)", "for", "A", "carriers", "vs.", "GG.", "The", "positive", "association", "between", "-509", "C", "allele", "and", "risk", "of", "CRC", "was", "more", "obvious", "when", "subgroup", "analyses", "were", "conducted", "for", "population-based", "and", "large", "sample-sized", "studies", "as", "well", "as", "Caucasians.", "In", "contrast,", "we", "did", "not", "observed", "any", "associations", "between", "TGF-β1", " ", "+869", "T", ">", "C,", "+915", "G", ">", "C,", "and", "risk", "of", "CRC.", "This", "study", "indicated", "that", "C", "allele", "of", "TGF-β1-509", "C", ">", "T", "and", "A", "allele", "of", "-800", "G", ">", "A", "might", "contribute", "to", "the", "increased", "risk", "of", "CRC,", "and", "could", "be", "used", "as", "two", "of", "genetic", "marks", "for", "screening", "individuals", "at", "high", "risk", "of", "CRC.", "Because", "of", "modest", "limitation,", "large", "sample-sized", "studies", "were", "required", "to", "confirm", "the", "findings." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 3, 4, 4, 4, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 3, 4, 4, 4, 0, 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The associations between four common genetic polymorphisms of transforming growth factor-β1 ( TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers vs. TT for -509 C > T, 1.03 for C carriers vs. TT for +869 T > C, 1.09 for C carriers vs. GG for +915 G > C -509 C > T , +869 T > C , +915 G > C, and -800 G > A) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 -800 G > A ) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 -509 C > T, +869 T > C -509 C > T , +869 T > C, +915 G > C , and -800 G > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers vs. TT for -509 C > T, 1.03 for C carriers vs. TT for +869 T > C +915 G > C , and -800 G > A) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers vs. TT for -509 C > T, 1.03 for C carriers vs. TT for +869 T > C, 1.09 for C carriers vs. GG for +915 G > C, and 1.19 for A carriers vs. GG for 800 G > A). However, C allele of TGF-β1 -509 C > T and A allele of -800 G > A were associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was 1.23 (0.99-1.52) for CC vs. TT for -509 C > T and 6.64 (3.46-12.72) for A carriers vs. GG. The positive association between -509 C allele and risk of CRC was more obvious when subgroup analyses were conducted for population-based and large sample-sized studies as well as Caucasians. In contrast, we did not observed any associations between TGF-β1   +869 T > C, +915 G > C, and risk of CRC. This study indicated that C allele of TGF-β1-509 C > T and A allele of -800 G > A might contribute to the increased risk of CRC, and could be used as two of genetic marks for screening individuals at high risk of CRC. Because of modest limitation, large sample-sized studies were required to confirm the findings.
[ 2, 1920, 5253, 2192, 3006, 3059, 3299, 8321, 1927, 13231, 2905, 2991, 17, 8603, 12, 5525, 17, 8603, 17, 30468, 45, 34, 62, 16, 15, 5713, 1026, 62, 34, 45, 16, 15, 6550, 1015, 49, 34, 45, 16, 1930, 17, 9658, 49, 34, 43, 13, 1930, 2565, 1927, 7820, 2798, 12, 2710, 16530, 1930, 2539, 13, 2162, 2252, 5673, 3942, 18, 1942, 5699, 16, 2239, 4355, 2578, 1998, 3322, 2882, 1927, 11756, 2274, 2568, 18, 2842, 16, 2038, 3609, 43, 5880, 17, 2333, 1942, 2520, 2634, 1920, 5253, 18, 2038, 11415, 1920, 8506, 1927, 15406, 16, 18319, 16, 1930, 9223, 29644, 1029, 1942, 3512, 8526, 2351, 16, 1930, 16760, 15623, 1982, 1990, 8555, 21, 16, 3775, 18, 6408, 3400, 12, 2014, 13, 1930, 3002, 9, 5203, 4979, 12, 3002, 9, 3371, 13, 1985, 3561, 1942, 2481, 1920, 5253, 18, 2342, 5880, 17, 2333, 3391, 1988, 5525, 17, 8603, 17, 30468, 45, 34, 62, 16, 15, 5713, 1026, 62, 34, 45, 16, 15, 6550, 1015, 49, 34, 45, 16, 1930, 17, 9658, 49, 34, 43, 1985, 2084, 2458, 1956, 2565, 1927, 7820, 16530, 12, 2014, 33, 20, 18, 5792, 1958, 45, 8974, 3201, 18, 7382, 1958, 17, 30468, 45, 34, 62, 16, 21, 18, 5167, 1958, 45, 8974, 3201, 18, 7382, 1958, 15, 5713, 1026, 62, 34, 45, 16, 21, 18, 7102, 1958, 45, 8974, 3201, 18, 12358, 1958, 15, 6550, 1015, 49, 34, 45, 17, 30468, 45, 34, 62, 16, 15, 5713, 1026, 62, 34, 45, 16, 15, 6550, 1015, 49, 34, 45, 16, 1930, 17, 9658, 49, 34, 43, 13, 1930, 2565, 1927, 7820, 2798, 12, 2710, 16530, 1930, 2539, 13, 2162, 2252, 5673, 3942, 18, 1942, 5699, 16, 2239, 4355, 2578, 1998, 3322, 2882, 1927, 11756, 2274, 2568, 18, 2842, 16, 2038, 3609, 43, 5880, 17, 2333, 1942, 2520, 2634, 1920, 5253, 18, 2038, 11415, 1920, 8506, 1927, 15406, 16, 18319, 16, 1930, 9223, 29644, 1029, 1942, 3512, 8526, 2351, 16, 1930, 16760, 15623, 1982, 1990, 8555, 21, 16, 3775, 18, 6408, 3400, 12, 2014, 13, 1930, 3002, 9, 5203, 4979, 12, 3002, 9, 3371, 13, 1985, 3561, 1942, 2481, 1920, 5253, 18, 2342, 5880, 17, 2333, 3391, 1988, 5525, 17, 8603, 17, 9658, 49, 34, 43, 13, 1930, 2565, 1927, 7820, 2798, 12, 2710, 16530, 1930, 2539, 13, 2162, 2252, 5673, 3942, 18, 1942, 5699, 16, 2239, 4355, 2578, 1998, 3322, 2882, 1927, 11756, 2274, 2568, 18, 2842, 16, 2038, 3609, 43, 5880, 17, 2333, 1942, 2520, 2634, 1920, 5253, 18, 2038, 11415, 1920, 8506, 1927, 15406, 16, 18319, 16, 1930, 9223, 29644, 1029, 1942, 3512, 8526, 2351, 16, 1930, 16760, 15623, 1982, 1990, 8555, 21, 16, 3775, 18, 6408, 3400, 12, 2014, 13, 1930, 3002, 9, 5203, 4979, 12, 3002, 9, 3371, 13, 1985, 3561, 1942, 2481, 1920, 5253, 18, 2342, 5880, 17, 2333, 3391, 1988, 5525, 17, 8603, 17, 30468, 45, 34, 62, 16, 15, 5713, 1026, 62, 34, 45, 17, 30468, 45, 34, 62, 16, 15, 5713, 1026, 62, 34, 45, 16, 15, 6550, 1015, 49, 34, 45, 16, 1930, 17, 9658, 49, 34, 43, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 3, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 3, 4, 4, 4, 4, -100 ]
20725929
[ "The", "MUTYH", "gene", "encodes", "a", "DNA", "glycosylase", "involved", "in", "base", "excision", "repair", "(BER).", "Biallelic", "pathogenic", "MUTYH", "variants", "have", "been", "associated", "with", "colorectal", "polyposis", "and", "cancer.", "The", "pathogenicity", "of", "a", "few", "variants", "is", "beyond", "doubt,", "including", "c.536A4G/p.Tyr179Cys", "and", "c.1187G4A/p.Gly396Asp", "(previously", "c.494A4G", "/", "p.Tyr165Cys", " ", "and", "c.1145G4A/", "p.Gly382Asp", ").However,", "for", "a", "substantial", "fraction", "of", "the", "detected", "variants,", "the", "clinical", "significance", "remains", "uncertain,compromising", "molecular", "diagnostics", "and", "thereby", "genetic", "counseling.", "We", "have", "established", "an", "interactive", "MUTYH", "gene", "sequence", "variant", "database", "(www.lovd.nl/MUTYH)", "with", "the", "aim", "of", "collecting", "and", "sharing", "MUTYH", "genotype", "and", "phenotype", "data", "worldwide.", "To", "support", "standard", "variant", "description,", "we", "chose", "NM_001128425.1", "as", "the", "reference", "sequence.", "The", "database", "includes", "records", "with", "variants", "per", "individual,", "linked", "to", "available", "phenotype", "and", "geographic", "origin", "data", "as", "well", "as", "records", "with", "in", "vitro", "functional", "and", "in", "silico", "test", "data.", "As", "of", "April", "2010,", "the", "database", "contains", "1968", "published", "and", "423", "unpublished", "submitted", "entries,", "and", "230", "and", "61", "unique", "variants,respectively.", "This", "open-access", "repository", "allows", "all", "involved", "to", "quickly", "share", "all", "variants", "encountered", "and", "communicate", "potential", "consequences,", "which", "will", "be", "especially", "useful", "to", "classify", "variants", "MUTYH", "c.1145G4A", "/p.Gly382Asp).However,", "for", "a", "substantial", "fraction", "of", "the", "detected", "variants,", "the", "clinical", "significance", "remains", "uncertain,compromising", "molecular", "diagnostics", "and", "thereby", "genetic", "counseling.", "We", "have", "established", "an", "interactive", "MUTYH", "gene", "sequence", "variant", "database", "(www.lovd.nl/MUTYH)", "with", "the", "aim", "of", "collecting", "and", "sharing", "MUTYH", "genotype", "and", "phenotype", "data", "worldwide.", "To", "support", "standard", "variant", "variants", ",", "the", "clinical", "significance", "remains", "uncertain,compromising", "molecular", "diagnostics", "and", "thereby", "genetic", "counseling.", "We", "have", "established", "an", "interactive", "MUTYH", "gene", "sequence", "variant", "database", "(www.lovd.nl/MUTYH)", "with", "the", "aim", "of", "collecting", "and", "sharing", "MUTYH", "genotype", "and", "phenotype", "data", "worldwide.", "To", "support", "standard", "variant", "description,", "we", "chose", "NM_001128425.1", "MUTYH", "variants", "MUTYH", " ", "gene." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 13, 0, 0, 0, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 3, 1, 0, 0 ]
The MUTYH gene encodes a DNA glycosylase involved in base excision repair (BER). Biallelic pathogenic MUTYH variants have been associated with colorectal polyposis and cancer. The pathogenicity of a few variants is beyond doubt, including c.536A4G/p.Tyr179Cys and c.1187G4A/p.Gly396Asp (previously c.494A4G / p.Tyr165Cys and c.1145G4A/ p.Gly382Asp ).However, for a substantial fraction of the detected variants, the clinical significance remains uncertain,compromising molecular diagnostics and thereby genetic counseling. We have established an interactive MUTYH gene sequence variant database (www.lovd.nl/MUTYH) with the aim of collecting and sharing MUTYH genotype and phenotype data worldwide. To support standard variant description, we chose NM_001128425.1 as the reference sequence. The database includes records with variants per individual, linked to available phenotype and geographic origin data as well as records with in vitro functional and in silico test data. As of April 2010, the database contains 1968 published and 423 unpublished submitted entries, and 230 and 61 unique variants,respectively. This open-access repository allows all involved to quickly share all variants encountered and communicate potential consequences, which will be especially useful to classify variants MUTYH c.1145G4A /p.Gly382Asp).However, for a substantial fraction of the detected variants, the clinical significance remains uncertain,compromising molecular diagnostics and thereby genetic counseling. We have established an interactive MUTYH gene sequence variant database (www.lovd.nl/MUTYH) with the aim of collecting and sharing MUTYH genotype and phenotype data worldwide. To support standard variant variants , the clinical significance remains uncertain,compromising molecular diagnostics and thereby genetic counseling. We have established an interactive MUTYH gene sequence variant database (www.lovd.nl/MUTYH) with the aim of collecting and sharing MUTYH genotype and phenotype data worldwide. To support standard variant description, we chose NM_001128425.1 MUTYH variants MUTYH gene.
[ 2, 1920, 2446, 1012, 1023, 2359, 9937, 43, 2678, 20067, 2051, 3286, 1922, 5170, 10940, 5059, 12, 8310, 13, 18, 27888, 1952, 3742, 8070, 2446, 1012, 1023, 4936, 2162, 2252, 2458, 1956, 7820, 28641, 1930, 2539, 18, 1920, 15903, 1927, 43, 3855, 4936, 1977, 6844, 19511, 16, 2710, 45, 18, 4522, 11084, 1006, 1029, 19, 58, 18, 9036, 25229, 23159, 1930, 45, 18, 10297, 1027, 21784, 1019, 19, 58, 18, 3376, 6021, 11084, 3508, 12, 3024, 45, 18, 30308, 16010, 1029, 19, 58, 18, 9036, 21597, 23159, 1930, 45, 18, 11296, 1015, 21784, 1019, 19, 58, 18, 3376, 4745, 5896, 3508, 13, 18, 2406, 16, 1958, 43, 6317, 3906, 1927, 1920, 3330, 4936, 16, 1920, 2535, 4550, 4497, 7323, 16, 24395, 3272, 12070, 1930, 6113, 3299, 12239, 18, 2038, 2162, 4379, 1925, 13974, 2446, 1012, 1023, 2359, 3244, 6031, 5039, 12, 6425, 18, 18412, 1007, 18, 9092, 19, 2446, 1012, 1023, 13, 1956, 1920, 3774, 1927, 13607, 1930, 10763, 2446, 1012, 1023, 5619, 1930, 4629, 2230, 8563, 18, 1942, 3373, 2970, 6031, 8418, 16, 2038, 10692, 2943, 41, 3472, 17818, 6852, 1015, 18, 21, 1966, 1920, 4386, 3244, 18, 1920, 5039, 5921, 7123, 1956, 4936, 2079, 2725, 16, 4624, 1942, 3322, 4629, 1930, 10579, 4853, 2230, 1966, 2486, 1966, 7123, 1956, 1922, 3596, 3183, 1930, 1922, 14270, 2648, 2230, 18, 1966, 1927, 11071, 3657, 16, 1920, 5039, 5461, 22553, 4586, 1930, 27286, 10858, 10568, 14992, 16, 1930, 14980, 1930, 5473, 5008, 4936, 16, 2763, 18, 2052, 4437, 17, 4065, 18868, 5731, 2136, 3286, 1942, 10521, 7948, 2136, 4936, 11989, 1930, 18606, 2889, 7080, 16, 2154, 2832, 1998, 4369, 4707, 1942, 14953, 4936, 2446, 1012, 1023, 45, 18, 11296, 1015, 21784, 1019, 19, 58, 18, 3376, 4745, 5896, 3508, 13, 18, 2406, 16, 1958, 43, 6317, 3906, 1927, 1920, 3330, 4936, 16, 1920, 2535, 4550, 4497, 7323, 16, 24395, 3272, 12070, 1930, 6113, 3299, 12239, 18, 2038, 2162, 4379, 1925, 13974, 2446, 1012, 1023, 2359, 3244, 6031, 5039, 12, 6425, 18, 18412, 1007, 18, 9092, 19, 2446, 1012, 1023, 13, 1956, 1920, 3774, 1927, 13607, 1930, 10763, 2446, 1012, 1023, 5619, 1930, 4629, 2230, 8563, 18, 1942, 3373, 2970, 6031, 4936, 16, 1920, 2535, 4550, 4497, 7323, 16, 24395, 3272, 12070, 1930, 6113, 3299, 12239, 18, 2038, 2162, 4379, 1925, 13974, 2446, 1012, 1023, 2359, 3244, 6031, 5039, 12, 6425, 18, 18412, 1007, 18, 9092, 19, 2446, 1012, 1023, 13, 1956, 1920, 3774, 1927, 13607, 1930, 10763, 2446, 1012, 1023, 5619, 1930, 4629, 2230, 8563, 18, 1942, 3373, 2970, 6031, 8418, 16, 2038, 10692, 2943, 41, 3472, 17818, 6852, 1015, 18, 21, 2446, 1012, 1023, 4936, 2446, 1012, 1023, 2359, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 0, 13, 14, 14, 14, 14, 0, 0, 0, 0, 0, 0, 0, 0, 13, 14, 14, 14, 14, 14, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 2, 2, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 2, 2, 2, 1, 2, 2, 3, 1, 2, 2, 0, 0, -100 ]
20196079
[ "Recent", "studies", "have", "suggested", "that", "APC", "loss", " ", "alone", "may", "be", "insufficient", "to", "promote", "aberrant", "Wnt/beta-catenin", "signalling.", "Our", "aim", "was", "to", "comprehensively", "characterize", "Wnt", "signalling", "components", "in", "a", "set", "of", "APC-associated", "familial", "adenomatous", "polyposis", "(FAP)", "tumours.", "Sixty", "adenomas", "from", "six", "FAP", "patients", "with", "known", "pathogenic", "APC", "mutations", "were", "included.", "Somatic", "APC", "and", "KRAS", "mutations,", "beta-catenin", "immunostaining,", "and", "qRT-PCR", "of", "APC,", "MYC,", "AXIN2", "and", "SFRP1", "were", "analysed.", "Array-comparative", "genomic", "hybridization", "(aCGH)", "was", "also", "assessed", "in", "26", "FAP", "adenomas", "and", "24", "paired", "adenoma-carcinoma", "samples.", "A", "somatic", "APC", "alteration", "was", "present", "in", "15", "adenomas", "(LOH", "in", "11", "and", "four", "point", "mutations).", "KRAS", "mutations", "were", "detected", "in", "10%", "of", "the", "cases.", "APC", "mRNA", "was", "overexpressed", "in", "adenomas.", "MYC", "and", "AXIN2", "were", "also", "overexpressed,", "with", "significant", "intra-case", "heterogeneity.", "Increased", "cytoplasmic", "and/or", "nuclear", "beta-catenin", "staining", "was", "seen", "in", "94%", "and", "80%", "of", "the", "adenomas.", "beta-Catenin", "nuclear", "staining", "was", "strongly", "associated", "with", "MYC", "levels", "(p", "value", "0.03)", "but", "not", "with", "KRAS", "mutations.", "Copy", "number", "aberrations", "were", "rare.", "However,", "the", "recurrent", "chromosome", "changes", "observed", "more", "frequently", "contained", "Wnt", "pathway", "genes", "(p", "value", "0.012).", "Based", "on", "beta-catenin", "staining", "and", "Wnt", "pathway", "target", "genes", "alterations", "the", "Wnt", "pathway", "appears", "to", "be", "constitutively", "activated", "in", "all", "APC-FAP", "tumours,", "with", "alterations", "occurring", "both", "upstream", "and", "downstream", "of", "APC.", "Wnt", "aberrations", "are", "present", "at", "both", "the", "DNA", "and", "the", "RNA", "level.", "Somatic", "profiling", "of", "APC", "APC", " ", "and", "KRAS", "mutations", "KRAS", " ", "mutations,", "beta-catenin", "immunostaining,", "and", "qRT-PCR", "of", "APC", ",", "MYC", ",", "AXIN2", " ", "and", "SFRP1", "APC", "-associated", "FAP", "adenomas." ]
[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0, 0, 0, 3, 1, 0, 0, 0, 0, 0, 0, 0, 1, 0, 1, 0, 1, 0, 0, 1, 1, 0, 0, 0 ]
Recent studies have suggested that APC loss alone may be insufficient to promote aberrant Wnt/beta-catenin signalling. Our aim was to comprehensively characterize Wnt signalling components in a set of APC-associated familial adenomatous polyposis (FAP) tumours. Sixty adenomas from six FAP patients with known pathogenic APC mutations were included. Somatic APC and KRAS mutations, beta-catenin immunostaining, and qRT-PCR of APC, MYC, AXIN2 and SFRP1 were analysed. Array-comparative genomic hybridization (aCGH) was also assessed in 26 FAP adenomas and 24 paired adenoma-carcinoma samples. A somatic APC alteration was present in 15 adenomas (LOH in 11 and four point mutations). KRAS mutations were detected in 10% of the cases. APC mRNA was overexpressed in adenomas. MYC and AXIN2 were also overexpressed, with significant intra-case heterogeneity. Increased cytoplasmic and/or nuclear beta-catenin staining was seen in 94% and 80% of the adenomas. beta-Catenin nuclear staining was strongly associated with MYC levels (p value 0.03) but not with KRAS mutations. Copy number aberrations were rare. However, the recurrent chromosome changes observed more frequently contained Wnt pathway genes (p value 0.012). Based on beta-catenin staining and Wnt pathway target genes alterations the Wnt pathway appears to be constitutively activated in all APC-FAP tumours, with alterations occurring both upstream and downstream of APC. Wnt aberrations are present at both the DNA and the RNA level. Somatic profiling of APC APC and KRAS mutations KRAS mutations, beta-catenin immunostaining, and qRT-PCR of APC , MYC , AXIN2 and SFRP1 APC -associated FAP adenomas.
[ 2, 3505, 2351, 2162, 3978, 1988, 9187, 3257, 4298, 2278, 1998, 9406, 1942, 5527, 9801, 7028, 19, 4666, 17, 7723, 8076, 18, 2342, 3774, 1982, 1942, 21183, 8063, 7028, 8076, 4178, 1922, 43, 2735, 1927, 9187, 17, 2458, 11444, 30390, 28641, 12, 20592, 13, 9313, 18, 14063, 16787, 2037, 3798, 20592, 2132, 1956, 3171, 8070, 9187, 3527, 1985, 3063, 18, 8548, 9187, 1930, 11083, 3527, 16, 4666, 17, 7723, 10930, 16, 1930, 10002, 17, 3343, 1927, 9187, 16, 5078, 16, 19911, 9090, 1930, 29998, 5113, 1985, 6450, 18, 6472, 17, 8255, 4935, 8335, 12, 28790, 1023, 13, 1982, 2222, 3683, 1922, 3179, 20592, 16787, 1930, 2686, 7304, 16530, 17, 5373, 2785, 18, 43, 8548, 9187, 10076, 1982, 2481, 1922, 2461, 16787, 12, 19716, 1922, 2513, 1930, 3006, 3575, 3527, 13, 18, 11083, 3527, 1985, 3330, 1922, 2119, 9, 1927, 1920, 2919, 18, 9187, 3616, 1982, 10593, 1922, 16787, 18, 5078, 1930, 19911, 9090, 1985, 2222, 10593, 16, 1956, 2228, 5153, 17, 3087, 6808, 18, 2502, 6823, 1930, 19, 2014, 4254, 4666, 17, 7723, 4166, 1982, 3945, 1922, 5650, 9, 1930, 3729, 9, 1927, 1920, 16787, 18, 4666, 17, 7723, 4254, 4166, 1982, 4937, 2458, 1956, 5078, 2428, 12, 58, 3113, 20, 18, 5167, 13, 2308, 2084, 1956, 11083, 3527, 18, 6983, 2529, 16303, 1985, 5844, 18, 2406, 16, 1920, 7457, 5597, 2840, 2528, 2253, 5467, 5543, 7028, 3374, 2628, 12, 58, 3113, 20, 18, 14632, 13, 18, 2454, 1990, 4666, 17, 7723, 4166, 1930, 7028, 3374, 2758, 2628, 5996, 1920, 7028, 3374, 5107, 1942, 1998, 11744, 4128, 1922, 2136, 9187, 17, 20592, 9313, 16, 1956, 5996, 6966, 2321, 7671, 1930, 5863, 1927, 9187, 18, 7028, 16303, 2032, 2481, 2019, 2321, 1920, 2678, 1930, 1920, 3146, 2237, 18, 8548, 10156, 1927, 9187, 9187, 1930, 11083, 3527, 11083, 3527, 16, 4666, 17, 7723, 10930, 16, 1930, 10002, 17, 3343, 1927, 9187, 16, 5078, 16, 19911, 9090, 1930, 29998, 5113, 9187, 17, 2458, 20592, 16787, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0, 0, 3, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 1, 0, 1, 2, 0, 1, 2, 1, 0, 0, 0, 0, 0, -100 ]
20646601
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
25029911
[ "##", "CONCLUSION" ]
[ 0, 0 ]
## CONCLUSION
[ 2, 7, 7, 4180, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
12534642
[ "In", "114", "samples,", "the", "most", "frequent", "CYP1A2", "SNPs", "were", "1545T-->C", "(38.2%", "of", "tested", "chromosomes),", "-164A-->C", "(CYP1A2*1F,", "33.3%)", "and", "-2464T-->delT", "(CYP1A2*1D,", "4.82%).", "The", "SNPs", "were", "in", "linkage", "disequilibrium:", "the", "most", "frequent", "constellations", "were", "found", "to", "be", "-3858G/-2464T/-740T/-164A/63C/1545T", "(61.8%),", "-3858G/-2464T/-740T/-164C/63C/1545C", "(33.3%),", "and", "-3858G/-2464delT/-740T/-164A/63C/1545C", "(3.51%),", "with", "no", "significant", "frequency", "differences", "between", "cases", "and", "controls.", "In", "the", "phenotype", "analysis,", "lower", "caffeine", "metabolic", "ratios", "were", "detected", "in", "cases", "than", "in", "controls.", "This", "was", "significant", "in", "smokers", "(n", "=", "14,", "P", "=", "0.020),", "and", "in", "a", "subgroup", "of", "15", "matched", "case-control", "pairs", "(P", "=", "0.007),", "but", "it", "was", "not", "significant", "in", "nonsmokers", "(n", "=", "100,", "P", "=", "0.39).", "There", "was", "no", "detectable", "association", "between", "CYP1A2", "genotype", "and", "caffeine", "phenotype." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
In 114 samples, the most frequent CYP1A2 SNPs were 1545T-->C (38.2% of tested chromosomes), -164A-->C (CYP1A2*1F, 33.3%) and -2464T-->delT (CYP1A2*1D, 4.82%). The SNPs were in linkage disequilibrium: the most frequent constellations were found to be -3858G/-2464T/-740T/-164A/63C/1545T (61.8%), -3858G/-2464T/-740T/-164C/63C/1545C (33.3%), and -3858G/-2464delT/-740T/-164A/63C/1545C (3.51%), with no significant frequency differences between cases and controls. In the phenotype analysis, lower caffeine metabolic ratios were detected in cases than in controls. This was significant in smokers (n = 14, P = 0.020), and in a subgroup of 15 matched case-control pairs (P = 0.007), but it was not significant in nonsmokers (n = 100, P = 0.39). There was no detectable association between CYP1A2 genotype and caffeine phenotype.
[ 2, 1922, 11296, 2785, 16, 1920, 2501, 6439, 6120, 23750, 6084, 1985, 14396, 1015, 1031, 17, 17, 34, 45, 12, 3738, 18, 22, 9, 1927, 3620, 8597, 13, 16, 17, 15170, 1019, 17, 17, 34, 45, 12, 6120, 23750, 14, 14078, 16, 3401, 18, 23, 9, 13, 1930, 17, 21141, 1006, 1031, 17, 17, 34, 17496, 12, 6120, 23750, 14, 8046, 16, 24, 18, 6175, 9, 13, 18, 1920, 6084, 1985, 1922, 8611, 19264, 30, 1920, 2501, 6439, 4713, 30439, 1036, 1985, 2435, 1942, 1998, 17, 25800, 1025, 1029, 19, 17, 21141, 1006, 1031, 19, 17, 5446, 1008, 1031, 19, 17, 15170, 1019, 19, 4968, 1030, 19, 14396, 1015, 1031, 12, 5473, 18, 28, 9, 13, 16, 17, 25800, 1025, 1029, 19, 17, 21141, 1006, 1031, 19, 17, 5446, 1008, 1031, 19, 17, 15170, 1030, 19, 4968, 1030, 19, 14396, 20118, 12, 3401, 18, 23, 9, 13, 16, 1930, 17, 25800, 1025, 1029, 19, 17, 21141, 28660, 9551, 19, 17, 5446, 1008, 1031, 19, 17, 15170, 1019, 19, 4968, 1030, 19, 14396, 20118, 12, 23, 18, 4892, 9, 13, 16, 1956, 2239, 2228, 3528, 2886, 2192, 2919, 1930, 3562, 18, 1922, 1920, 4629, 2333, 16, 2826, 14119, 4487, 5835, 1985, 3330, 1922, 2919, 2254, 1922, 3562, 18, 2052, 1982, 2228, 1922, 8112, 12, 56, 33, 2607, 16, 58, 33, 20, 18, 18773, 13, 16, 1930, 1922, 43, 6200, 1927, 2461, 5992, 3087, 17, 2285, 5803, 12, 58, 33, 20, 18, 13298, 13, 16, 2308, 2176, 1982, 2084, 2228, 1922, 28500, 12, 56, 33, 2813, 16, 58, 33, 20, 18, 3886, 13, 18, 2276, 1982, 2239, 7398, 3279, 2192, 6120, 23750, 5619, 1930, 14119, 4629, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14645426
[ "##", "PATIENTS", "AND", "METHODS" ]
[ 0, 0, 0, 0 ]
## PATIENTS AND METHODS
[ 2, 7, 7, 2132, 1930, 2860, 3 ]
[ 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, -100 ]
26925673
[ "##", "PURPOSE" ]
[ 0, 0 ]
## PURPOSE
[ 2, 7, 7, 5120, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
22899730
[ "Among", "1,980", "cases", "tested,", "12%", "were", "BRAF", "c.1799T>A", "(p.V600E)", "mutation", "c.1799T>A", "microsatellite", "instability", " ", "(MSI)", "and", "are", "associated", "with", "other", "prognostic", "factors.", "The", "independent", "association", "between", "BRAF", "mutation", "status", "and", "CRC", "survival,", "however,", "remains", "unclear." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 3, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation c.1799T>A microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear.
[ 2, 2706, 21, 16, 28399, 2919, 3620, 16, 2369, 9, 1985, 11346, 45, 18, 16182, 1026, 1031, 34, 43, 12, 58, 18, 23727, 13, 3979, 45, 18, 16182, 1026, 1031, 34, 43, 16069, 9557, 12, 17355, 13, 1930, 2032, 2458, 1956, 2303, 6750, 2790, 18, 1920, 3484, 3279, 2192, 11346, 3979, 3642, 1930, 8223, 3298, 16, 2406, 16, 4497, 6390, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 3, 4, 4, 4, 4, 4, 4, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
22545919
[ "We", "evaluated", "associations", "of", "putative", "regulatory", "single", "nucleotide", "polymorphisms", "(SNPs)", "in", "genes", "from", "the", "oxidative", "phosphorylation", "chain", "with", "survival", "and", "disease", "prognosis", "in", "613", "CRC", "patients", "from", "Northern", "Germany", "(PopGen", "cohort)." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort).
[ 2, 2038, 3747, 5253, 1927, 6770, 4948, 2957, 5489, 8321, 12, 6084, 13, 1922, 2628, 2037, 1920, 5163, 4050, 4659, 1956, 3298, 1930, 2573, 6573, 1922, 5473, 1010, 8223, 2132, 2037, 9250, 6205, 12, 2640, 2432, 4382, 13, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
22899730
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
[ 2, 7, 7, 4355, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
26416897
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
[ 2, 7, 7, 4355, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
15702478
[ "Mutation", "analysis", "of", "p53,", "K-ras,", "and", "BRAF", "genes", "in", "colorectal", "cancer", "progression." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Mutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progression.
[ 2, 3979, 2333, 1927, 5105, 16, 53, 17, 6520, 16, 1930, 11346, 2628, 1922, 7820, 2539, 4380, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9731891
[ "Microsatellite", "instability", "mutations", "Microsatellite", "instability", " ", "and", "p53", "mutations", "in", "sporadic", "right", "and", "left", "colon", "carcinoma:", "different", "clinical", "and", "molecular", "implications.", "\n\n\n", "##", "BACKGROUND" ]
[ 3, 4, 3, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Microsatellite instability mutations Microsatellite instability and p53 mutations in sporadic right and left colon carcinoma: different clinical and molecular implications. ## BACKGROUND
[ 2, 16069, 9557, 3527, 16069, 9557, 1930, 5105, 3527, 1922, 13088, 3659, 1930, 3506, 4120, 5373, 30, 2413, 2535, 1930, 3272, 7020, 18, 7, 7, 3872, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 3, 4, 3, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
10822375
[ "Inactivation", " ", "of", "DNA-mismatch", "repair", "underlies", "the", "genesis", "of", "microsatellite", "unstable", "(MSI)", "colon", "cancers.", "hPMS2", "is", "one", "of", "several", "genes", "encoding", "components", "of", "the", "DNA-mismatch", "repair", "complex,", "and", "germline", "hPMS2", "mutations", "have", "been", "found", "in", "a", "few", "kindreds", "with", "hereditary", "nonpolyposis", "colorectal", "carcinoma", "(HNPCC),", "in", "whom", "hereditary", "MSI", "colon", "cancers", "develop.", "However,", "mice", "bearing", "null", "hPMS2", "genes", "do", "not", "develop", "colon", "cancers", "and", "hPMS2", "mutations", "in", "sporadic", "human", "colon", "cancers", "have", "not", "been", "described.", "Here", "we", "report", "that", "in", "Vaco481", "colon", "cancer", "the", "hPMS2", "gene", "is", "inactivated", "by", "somatic", "mutations", "of", "both", "hPMS2", "alleles.", "The", "cell", "line", "derived", "from", "this", "tumor", "is", "functionally", "deficient", "in", "DNA", "mismatch", "repair.", "This", "deficiency", "can", "be", "biochemically", "complemented", "by", "addition", "of", "a", "purified", "hMLH1-hPMS2", "(hMutLalpha)", "complex.", "The", "hPMS2", "deficient", "Vaco481", "cancer", "cell", "line", "demonstrates", "microsatellite", "instability,", "an", "elevated", "HPRT", "gene", "mutation", "rate,", "and", "resistance", "to", "the", "cytotoxicity", "of", "the", "alkylator", "MNNG.", "We", "conclude", "that", "somatic", "inactivation", "mutations", " ", "of", "both", "hPMS2", "alleles.", "The", "cell", "line", "derived", "from", "this", "tumor", "is", "functionally", "deficient", "in", "DNA", "mismatch", "repair.", "This", "deficiency", "can", "be", "biochemically", "complemented", "by", "addition", "of", "a", "purified", "hMLH1-hPMS2", "(hMutLalpha)", "complex.", "The", "hPMS2", "deficient", "Vaco481", "cancer", "cell", "line", "demonstrates", "microsatellite", "instability", "hPMS2", " ", "deficient", "Vaco481", "cancer", "cell", "line", "demonstrates", "microsatellite", "instability,", "an", "elevated", "HPRT", "gene", "mutation", "HPRT", " ", "gene", "mutation", "rate,", "and", "resistance", "to", "the", "cytotoxicity", "of", "the", "alkylator", "MNNG.", "We", "conclude", "that", "somatic", "inactivation", "of", "hPMS2", "can", "play", "a", "role", "in", "development", "of", "sporadic", "MSI", "hPMS2", "hPMS2", " ", "as", "a", "possible", "cause", "of", "sporadic", "human", "colon", "cancer", "with", "microsatellite", "instability." ]
[ 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Inactivation of DNA-mismatch repair underlies the genesis of microsatellite unstable (MSI) colon cancers. hPMS2 is one of several genes encoding components of the DNA-mismatch repair complex, and germline hPMS2 mutations have been found in a few kindreds with hereditary nonpolyposis colorectal carcinoma (HNPCC), in whom hereditary MSI colon cancers develop. However, mice bearing null hPMS2 genes do not develop colon cancers and hPMS2 mutations in sporadic human colon cancers have not been described. Here we report that in Vaco481 colon cancer the hPMS2 gene is inactivated by somatic mutations of both hPMS2 alleles. The cell line derived from this tumor is functionally deficient in DNA mismatch repair. This deficiency can be biochemically complemented by addition of a purified hMLH1-hPMS2 (hMutLalpha) complex. The hPMS2 deficient Vaco481 cancer cell line demonstrates microsatellite instability, an elevated HPRT gene mutation rate, and resistance to the cytotoxicity of the alkylator MNNG. We conclude that somatic inactivation mutations of both hPMS2 alleles. The cell line derived from this tumor is functionally deficient in DNA mismatch repair. This deficiency can be biochemically complemented by addition of a purified hMLH1-hPMS2 (hMutLalpha) complex. The hPMS2 deficient Vaco481 cancer cell line demonstrates microsatellite instability hPMS2 deficient Vaco481 cancer cell line demonstrates microsatellite instability, an elevated HPRT gene mutation HPRT gene mutation rate, and resistance to the cytotoxicity of the alkylator MNNG. We conclude that somatic inactivation of hPMS2 can play a role in development of sporadic MSI hPMS2 hPMS2 as a possible cause of sporadic human colon cancer with microsatellite instability.
[ 2, 8005, 1927, 2678, 17, 10265, 5059, 23268, 1920, 25309, 1927, 16069, 11976, 12, 17355, 13, 4120, 5717, 18, 4688, 2800, 1028, 1977, 2340, 1927, 2980, 2628, 5797, 4178, 1927, 1920, 2678, 17, 10265, 5059, 2796, 16, 1930, 12237, 4688, 2800, 1028, 3527, 2162, 2252, 2435, 1922, 43, 3855, 6925, 3510, 1036, 1956, 16321, 24857, 26558, 2420, 1937, 7820, 5373, 12, 9888, 7693, 1030, 13, 16, 1922, 8566, 16321, 17355, 4120, 5717, 2392, 18, 2406, 16, 2518, 8188, 6764, 4688, 2800, 1028, 2628, 2608, 2084, 2392, 4120, 5717, 1930, 4688, 2800, 1028, 3527, 1922, 13088, 2616, 4120, 5717, 2162, 2084, 2252, 2910, 18, 3410, 2038, 3809, 1988, 1922, 7017, 10047, 11425, 4120, 2539, 1920, 4688, 2800, 1028, 2359, 1977, 11588, 2007, 8548, 3527, 1927, 2321, 4688, 2800, 1028, 7096, 18, 1920, 2024, 2823, 3595, 2037, 2052, 2798, 1977, 9346, 5778, 1922, 2678, 10265, 5059, 18, 2052, 6179, 2112, 1998, 25839, 17849, 2007, 2459, 1927, 43, 4939, 5833, 1024, 8600, 17, 4688, 2800, 1028, 12, 5833, 1984, 5148, 13857, 2722, 13, 2796, 18, 1920, 4688, 2800, 1028, 5778, 7017, 10047, 11425, 2539, 2024, 2823, 7706, 16069, 9557, 16, 1925, 4664, 18542, 1031, 2359, 3979, 2769, 16, 1930, 3554, 1942, 1920, 8470, 1927, 1920, 13345, 3061, 5890, 2029, 18, 2038, 7676, 1988, 8548, 8005, 3527, 1927, 2321, 4688, 2800, 1028, 7096, 18, 1920, 2024, 2823, 3595, 2037, 2052, 2798, 1977, 9346, 5778, 1922, 2678, 10265, 5059, 18, 2052, 6179, 2112, 1998, 25839, 17849, 2007, 2459, 1927, 43, 4939, 5833, 1024, 8600, 17, 4688, 2800, 1028, 12, 5833, 1984, 5148, 13857, 2722, 13, 2796, 18, 1920, 4688, 2800, 1028, 5778, 7017, 10047, 11425, 2539, 2024, 2823, 7706, 16069, 9557, 4688, 2800, 1028, 5778, 7017, 10047, 11425, 2539, 2024, 2823, 7706, 16069, 9557, 16, 1925, 4664, 18542, 1031, 2359, 3979, 18542, 1031, 2359, 3979, 2769, 16, 1930, 3554, 1942, 1920, 8470, 1927, 1920, 13345, 3061, 5890, 2029, 18, 2038, 7676, 1988, 8548, 8005, 1927, 4688, 2800, 1028, 2112, 3918, 43, 2770, 1922, 2740, 1927, 13088, 17355, 4688, 2800, 1028, 4688, 2800, 1028, 1966, 43, 3216, 3936, 1927, 13088, 2616, 4120, 2539, 1956, 16069, 9557, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 2, 2, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
24576032
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
14734469
[ "##", "EXPERIMENTAL", "DESIGN" ]
[ 0, 0, 0 ]
## EXPERIMENTAL DESIGN
[ 2, 7, 7, 3599, 3036, 3 ]
[ 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, -100 ]
14734469
[ "##", "EXPERIMENTAL", "DESIGN" ]
[ 0, 0, 0 ]
## EXPERIMENTAL DESIGN
[ 2, 7, 7, 3599, 3036, 3 ]
[ 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, -100 ]
21261604
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
14645426
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
26302849
[ "Polymorphisms", "of", "PRLHR", "and", "HSPA12A", "and", "risk", "of", "gastric", "and", "colorectal", "cancer", "in", "the", "Chinese", "Han", "population.", "\n\n\n", "##", "BACKGROUND" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Polymorphisms of PRLHR and HSPA12A and risk of gastric and colorectal cancer in the Chinese Han population. ## BACKGROUND
[ 2, 8321, 1927, 15593, 6570, 1930, 6418, 4904, 5896, 1930, 2565, 1927, 6319, 1930, 7820, 2539, 1922, 1920, 7185, 13087, 2973, 18, 7, 7, 3872, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
22899730
[ "Among", "1,980", "cases", "tested,", "12%", "were", "BRAF", " ", "c.1799T>A", "(p.V600E)", "mutation-positive", "(n", "=", "247).", "BRAF", "-mutated", "CRC", "was", "associated", "with", "poorer", "disease-specific", "survival", "adjusting", "for", "age,", "sex,", "time", "from", "diagnosis", "to", "enrollment,", "stage,", "and", "MSI", "status", "(HR,", "1.43;", "95%", "CI,", "1.05-1.95).", "This", "association", "was", "limited", "to", "cases", "diagnosed", "at", "ages", "<50", "(HR,", "3.06;", "95%", "CI,", "1.70-5.52)", "and", "was", "not", "evident", "in", "cases", "with", "MSI", "mutated", " ", "CRC", "was", "associated", "with", "poorer", "disease-specific", "survival", "adjusting", "for", "age,", "sex,", "time", "from", "diagnosis", "to", "enrollment,", "stage,", "and", "MSI", "status", "(HR,", "1.43;", "95%", "CI,", "1.05-1.95).", "This", "association", "was", "limited", "to", "cases", "diagnosed", "at", "ages", "<50", "(HR,", "3.06;", "95%", "CI,", "1.70-5.52)", "and", "was", "not", "evident", "in", "cases", "with", "MSI-high", "tumors", "(HR,", "0.94;", "95%", "CI,", "0.44-2.03).", "Associations", "with", "overall", "survival", "were", "similar." ]
[ 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation-positive (n = 247). BRAF -mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70-5.52) and was not evident in cases with MSI mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70-5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44-2.03). Associations with overall survival were similar.
[ 2, 2706, 21, 16, 28399, 2919, 3620, 16, 2369, 9, 1985, 11346, 45, 18, 16182, 1026, 1031, 34, 43, 12, 58, 18, 23727, 13, 3979, 17, 2843, 12, 56, 33, 20892, 13, 18, 11346, 17, 8336, 8223, 1982, 2458, 1956, 11667, 2573, 17, 2487, 3298, 9772, 1958, 2632, 16, 3486, 16, 2367, 2037, 3574, 1942, 11811, 16, 3587, 16, 1930, 17355, 3642, 12, 3668, 16, 21, 18, 3941, 31, 3002, 9, 3371, 16, 21, 18, 2914, 17, 21, 18, 3002, 13, 18, 2052, 3279, 1982, 3892, 1942, 2919, 5377, 2019, 7684, 32, 2761, 12, 3668, 16, 23, 18, 6604, 31, 3002, 9, 3371, 16, 21, 18, 3895, 17, 25, 18, 4764, 13, 1930, 1982, 2084, 7501, 1922, 2919, 1956, 17355, 8336, 8223, 1982, 2458, 1956, 11667, 2573, 17, 2487, 3298, 9772, 1958, 2632, 16, 3486, 16, 2367, 2037, 3574, 1942, 11811, 16, 3587, 16, 1930, 17355, 3642, 12, 3668, 16, 21, 18, 3941, 31, 3002, 9, 3371, 16, 21, 18, 2914, 17, 21, 18, 3002, 13, 18, 2052, 3279, 1982, 3892, 1942, 2919, 5377, 2019, 7684, 32, 2761, 12, 3668, 16, 23, 18, 6604, 31, 3002, 9, 3371, 16, 21, 18, 3895, 17, 25, 18, 4764, 13, 1930, 1982, 2084, 7501, 1922, 2919, 1956, 17355, 17, 2149, 3861, 12, 3668, 16, 20, 18, 5650, 31, 3002, 9, 3371, 16, 20, 18, 4044, 17, 22, 18, 5167, 13, 18, 5253, 1956, 3399, 3298, 1985, 2551, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9841584
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
23132392
[ "##", "CONCLUSION" ]
[ 0, 0 ]
## CONCLUSION
[ 2, 7, 7, 4180, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
24225759
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
26302849
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
22899730
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
19706845
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
17938238
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
17007003
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
18345036
[ "Deregulation", "of", "Cdk2", "causes", "Bim-mediated", "apoptosis", "in", "p53-deficient", "tumors", "following", "actin", "damage." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage.
[ 2, 22089, 1927, 18664, 5092, 11753, 17, 3434, 4091, 1922, 5105, 17, 5778, 3861, 2894, 4718, 4293, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
25029911
[ "We", "defined", "the", "minimal", "promoter", "of", "NGX6", "gene", "in", "a", "186-bp", "region", "(from-86", "to", "+100)", "through", "mutation", "construct", "methods", "and", "luciferase", "assays.", "Results", "from", "Electrophoretic", "mobility", "shift", "assays", "(EMSA)", "and", "Chromatin", "immunoprecipitation", "(ChIP)", "revealed", "that", "Early", "growth", "response", "gene", "1", "(Egr-1)", "binds", "to", "the", "Sp1/Egr-1", "overlapping", "site", "of", "NGX6", " ", "minimal", "promoter.", "Overexpression", "of", "Egr-1", "increased", "the", "promoter", "activity", "and", "mRNA", "level", "of", "NGX6", "gene;", "while", "knock-down", "of", "endogenous", "Egr-1", "decreased", "mRNA", "expression", "of", "NGX6", "gene." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
We defined the minimal promoter of NGX6 gene in a 186-bp region (from-86 to +100) through mutation construct methods and luciferase assays. Results from Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) revealed that Early growth response gene 1 (Egr-1) binds to the Sp1/Egr-1 overlapping site of NGX6 minimal promoter. Overexpression of Egr-1 increased the promoter activity and mRNA level of NGX6 gene; while knock-down of endogenous Egr-1 decreased mRNA expression of NGX6 gene.
[ 2, 2038, 3608, 1920, 6343, 4465, 1927, 4375, 20649, 2359, 1922, 43, 16524, 17, 4149, 3031, 12, 2037, 17, 5713, 1942, 15, 2813, 13, 2596, 3979, 6377, 2860, 1930, 7362, 4614, 18, 2274, 2037, 18658, 8471, 5950, 4614, 12, 22800, 13, 1930, 6338, 10253, 12, 7333, 13, 3404, 1988, 3120, 2905, 2644, 2359, 21, 12, 15850, 17, 21, 13, 6876, 1942, 1920, 15847, 19, 15850, 17, 21, 8984, 3200, 1927, 4375, 20649, 6343, 4465, 18, 5616, 1927, 15850, 17, 21, 2502, 1920, 4465, 2455, 1930, 3616, 2237, 1927, 4375, 20649, 2359, 31, 2679, 4556, 17, 3292, 1927, 5355, 15850, 17, 21, 3261, 3616, 2294, 1927, 4375, 20649, 2359, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9841584
[ "Decision", "analysis", "model.", "Lifetime", "risk", "for", "colorectal", "cancer,", "efficacy", "of", "surveillance", "and", "colectomy,", "stage-specific", "colorectal", "cancer", "mortality,", "and", "quality", "of", "life", "were", "included", "in", "the", "model." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Decision analysis model. Lifetime risk for colorectal cancer, efficacy of surveillance and colectomy, stage-specific colorectal cancer mortality, and quality of life were included in the model.
[ 2, 5534, 2333, 2322, 18, 9416, 2565, 1958, 7820, 2539, 16, 4348, 1927, 7889, 1930, 21481, 2341, 3542, 16, 3587, 17, 2487, 7820, 2539, 3885, 16, 1930, 3455, 1927, 3308, 1985, 3063, 1922, 1920, 2322, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
23603433
[ "Specific", "patterns", "of", "genomic", "aberrations", "have", "been", "associated", "with", "different", "types", "of", "malignancies.", "In", "colorectal", "cancer,", "losses", "of", "chromosome", "arm", "8p", "and", "gains", "of", "chromosome", "arm", "8q", "are", "among", "the", "most", "common", "chromosomal", "rearrangements,", "suggesting", "that", "the", "centromeric", "portion", "of", "chromosome", "8", "is", "particularly", "sensitive", "to", "breakage.", "Genomic", "alterations", "frequently", "occur", "in", "the", "early", "stages", "of", "tumorigenesis", "at", "specific", "genomic", "regions", "known", "as", "common", "fragile", "sites", "(cFSs).", "CFSs", " ", "represent", "parts", "of", "the", "normal", "chromosome", "structure", "that", "are", "prone", "to", "breakage", "under", "replication", "stress.", "In", "this", "study,", "we", "identified", "the", "genomic", "location", "of", "FRA8I,", "spanning", "530", "kb", "at", "8q11.21", "and", "assessed", "the", "composition", "of", "the", "fragile", "DNA", "sequence.", "FRA8I", "encompasses", "KIAA0146,", "a", "large", "protein-coding", "gene", "with", "yet", "unknown", "function,", "as", "well", "as", "CEBPD", "and", "part", "of", "PRKDC,", "two", "genes", "encoding", "proteins", "involved", "in", "tumorigenesis", "in", "a", "variety", "of", "cancers.", "We", "show", "that", "FRA8I", "is", "unstable", "in", "lymphocytes", "and", "epithelial", "cells,", "displaying", "similar", "expression", "rates.", "We", "examined", "copy", "number", "alteration", "patterns", "within", "FRA8I", "in", "a", "panel", "of", "25", "colorectal", "cancer", "cell", "lines", "and", "surveyed", "publically", "available", "profiles", "of", "56", "additional", "colorectal", "cancer", "cell", "lines.", "Combining", "these", "data", "shows", "that", "focal", "recombination", "events", "disrupt", "the", "genomic", "integrity", "of", "KIAA0146", "and", "neighboring", "cFS", "genes", "in", "12.3%", "of", "colorectal", "cancer", "cell", "lines.", "Moreover,", "data", "analysis", "revealed", "evidence", "that", "KIAA0146", "is", "a", "translocation", "partner", "of", "the", "immunoglobulin", "heavy", "chain", "gene", "in", "recurrent", "t(8;14)(q11;q32)", "translocations", "in", "a", "subset", "of", "patients", "with", "B-cell", "precursor", "acute", "lymphoblastic", "leukemia.", "Our", "data", "molecularly", "describe", "a", "region", "of", "enhanced", "chromosomal", "instability", "in", "the", "human", "genome", "and", "point", "to", "a", "role", "of", "the", "KIAA0146", "gene", "in", "tumorigenesis." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Specific patterns of genomic aberrations have been associated with different types of malignancies. In colorectal cancer, losses of chromosome arm 8p and gains of chromosome arm 8q are among the most common chromosomal rearrangements, suggesting that the centromeric portion of chromosome 8 is particularly sensitive to breakage. Genomic alterations frequently occur in the early stages of tumorigenesis at specific genomic regions known as common fragile sites (cFSs). CFSs represent parts of the normal chromosome structure that are prone to breakage under replication stress. In this study, we identified the genomic location of FRA8I, spanning 530 kb at 8q11.21 and assessed the composition of the fragile DNA sequence. FRA8I encompasses KIAA0146, a large protein-coding gene with yet unknown function, as well as CEBPD and part of PRKDC, two genes encoding proteins involved in tumorigenesis in a variety of cancers. We show that FRA8I is unstable in lymphocytes and epithelial cells, displaying similar expression rates. We examined copy number alteration patterns within FRA8I in a panel of 25 colorectal cancer cell lines and surveyed publically available profiles of 56 additional colorectal cancer cell lines. Combining these data shows that focal recombination events disrupt the genomic integrity of KIAA0146 and neighboring cFS genes in 12.3% of colorectal cancer cell lines. Moreover, data analysis revealed evidence that KIAA0146 is a translocation partner of the immunoglobulin heavy chain gene in recurrent t(8;14)(q11;q32) translocations in a subset of patients with B-cell precursor acute lymphoblastic leukemia. Our data molecularly describe a region of enhanced chromosomal instability in the human genome and point to a role of the KIAA0146 gene in tumorigenesis.
[ 2, 2487, 4147, 1927, 4935, 16303, 2162, 2252, 2458, 1956, 2413, 3584, 1927, 10672, 18, 1922, 7820, 2539, 16, 11783, 1927, 5597, 6011, 28, 1034, 1930, 13241, 1927, 5597, 6011, 28, 1055, 2032, 2706, 1920, 2501, 3059, 9220, 13955, 16, 3783, 1988, 1920, 25790, 7717, 1927, 5597, 28, 1977, 4443, 4532, 1942, 25816, 18, 4935, 5996, 5467, 4704, 1922, 1920, 3120, 5143, 1927, 11472, 2019, 2487, 4935, 3451, 3171, 1966, 3059, 19734, 3402, 12, 14653, 1036, 13, 18, 14653, 1036, 3015, 7516, 1927, 1920, 2791, 5597, 3170, 1988, 2032, 10424, 1942, 25816, 2441, 5158, 3071, 18, 1922, 2052, 2161, 16, 2038, 2899, 1920, 4935, 5185, 1927, 23228, 1025, 1033, 16, 13346, 21157, 6633, 2019, 28, 23931, 18, 2900, 1930, 3683, 1920, 5128, 1927, 1920, 19734, 2678, 3244, 18, 23228, 1025, 1033, 21569, 8191, 5025, 6924, 7772, 16, 43, 3103, 2213, 17, 5804, 2359, 1956, 4898, 5435, 2347, 16, 1966, 2486, 1966, 5827, 3846, 1007, 1930, 3131, 1927, 22615, 11385, 16, 2288, 2628, 5797, 2697, 3286, 1922, 11472, 1922, 43, 5386, 1927, 5717, 18, 2038, 2146, 1988, 23228, 1025, 1033, 1977, 11976, 1922, 7257, 1930, 4944, 2094, 16, 13867, 2551, 2294, 3389, 18, 2038, 3572, 6983, 2529, 10076, 4147, 2651, 23228, 1025, 1033, 1922, 43, 4812, 1927, 2637, 7820, 2539, 2024, 3557, 1930, 15544, 4462, 2169, 3322, 5554, 1927, 4489, 3281, 7820, 2539, 2024, 3557, 18, 9138, 2144, 2230, 3661, 1988, 8083, 7827, 3916, 12512, 1920, 4935, 7996, 1927, 8191, 5025, 6924, 7772, 1930, 12260, 14653, 2628, 1922, 2369, 18, 23, 9, 1927, 7820, 2539, 2024, 3557, 18, 3950, 16, 2230, 2333, 3404, 3095, 1988, 8191, 5025, 6924, 7772, 1977, 43, 7849, 8240, 1927, 1920, 11837, 7881, 4659, 2359, 1922, 7457, 62, 12, 28, 31, 2607, 13, 12, 22027, 1009, 31, 25760, 1028, 13, 22436, 1922, 43, 6728, 1927, 2132, 1956, 44, 17, 2024, 7897, 3939, 24403, 8111, 18, 2342, 2230, 26391, 5993, 43, 3031, 1927, 4256, 9220, 9557, 1922, 1920, 2616, 3843, 1930, 3575, 1942, 43, 2770, 1927, 1920, 8191, 5025, 6924, 7772, 2359, 1922, 11472, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9841584
[ "Immediate", "prophylactic", "colectomy;", "delayed", "colectomy", "on", "the", "basis", "of", "age,", "adenoma,", "or", "diagnosis", "of", "colorectal", "cancer;", "and", "endoscopic", "surveillance.", "Prophylactic", "surgical", "options", "were", "proctocolectomy", "with", "ileoanal", "anastomosis", "and", "subtotal", "colectomy", "with", "ileorectal", "anastomosis." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Immediate prophylactic colectomy; delayed colectomy on the basis of age, adenoma, or diagnosis of colorectal cancer; and endoscopic surveillance. Prophylactic surgical options were proctocolectomy with ileoanal anastomosis and subtotal colectomy with ileorectal anastomosis.
[ 2, 8426, 14847, 21481, 2341, 3542, 31, 7083, 21481, 2341, 3542, 1990, 1920, 4859, 1927, 2632, 16, 16530, 16, 2014, 3574, 1927, 7820, 2539, 31, 1930, 10448, 7889, 18, 14847, 4548, 8416, 1985, 9823, 4575, 4879, 25419, 4575, 14930, 1956, 9940, 6952, 3163, 17331, 1930, 13329, 10868, 21481, 2341, 3542, 1956, 9940, 28834, 17331, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
26925673
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
23132392
[ "Mediator", "complex", "participates", "in", "transcriptional", "regulation", "by", "connecting", "regulatory", "DNA", "sequences", "to", "the", "RNA", "polymerase", "II", "initiation", "complex.", "Recently,", "we", "discovered", "through", "exome", "sequencing", "that", "as", "many", "as", "70%", "of", "uterine", "leiomyomas", "harbour", "specific", "mutations", "in", "exon", "2", "of", "mediator", "complex", "subunit", "12", "(MED12).", "In", "this", "work,", "we", "examined", "the", "role", "of", "MED12", "exon", "2", "mutations", "in", "other", "tumour", "types." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Mediator complex participates in transcriptional regulation by connecting regulatory DNA sequences to the RNA polymerase II initiation complex. Recently, we discovered through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined the role of MED12 exon 2 mutations in other tumour types.
[ 2, 11370, 2796, 17241, 1922, 5224, 3640, 2007, 15031, 4948, 2678, 3709, 1942, 1920, 3146, 6479, 2890, 6035, 2796, 18, 3998, 16, 2038, 8117, 2596, 16390, 4754, 1988, 1966, 3086, 1966, 3895, 9, 1927, 10885, 22917, 4956, 20502, 2487, 3527, 1922, 7049, 22, 1927, 11370, 2796, 5903, 2369, 12, 2242, 3112, 13, 18, 1922, 2052, 2778, 16, 2038, 3572, 1920, 2770, 1927, 2242, 3112, 7049, 22, 3527, 1922, 2303, 6383, 3584, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
23132392
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
27070770
[ "to", "study", "the", "clinical", "organ-specific", "manifestations", "in", "patients", "with", "FAP", "and", "Peutz-Jeghers,", "genetics", "update", "and", "possibilities", "of", "diagnosis,", "monitoring,", "and", "treatment", "of", "these", "diseases." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
to study the clinical organ-specific manifestations in patients with FAP and Peutz-Jeghers, genetics update and possibilities of diagnosis, monitoring, and treatment of these diseases.
[ 2, 1942, 2161, 1920, 2535, 3090, 17, 2487, 10952, 1922, 2132, 1956, 20592, 1930, 2737, 24793, 17, 8988, 2509, 2045, 16, 10072, 15623, 1930, 13860, 1927, 3574, 16, 5378, 16, 1930, 2311, 1927, 2144, 3902, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14734469
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
14734469
[ "##", "EXPERIMENTAL", "DESIGN" ]
[ 0, 0, 0 ]
## EXPERIMENTAL DESIGN
[ 2, 7, 7, 3599, 3036, 3 ]
[ 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, -100 ]
17186357
[ "The", "GNAS1", "locus", "encodes", "the", "G(alpha)s", "protein", "which", "stimulates", "the", "formation", "of", "cyclic", "AMP", "(cAMP).", "Subsequently", "the", "cAMP", "pathway", "mediates", "various", "pleiotropic", "effects", "including", "regulation", "of", "apoptosis", "and", "proliferation.", "We", "have", "recently", "shown", "that", "genotypes", "of", "the", "single", "nucleotide", "polymorphism", " ", "(SNP)", "T393C", "SNP", ")", "T393C", "in", "the", "gene", "GNAS1", "are", "associated", "with", "survival", "of", "patients", "suffering", "from", "bladder,", "renal", "cell", "and", "colorectal", "carcinoma.", "In", "the", "present", "study,", "the", "genotypes", "of", "the", "T393C", "SNP", "were", "determined", "in", "279", "patients", "with", "invasive", "breast", "carcinoma.", "Comparing", "the", "genotypes", "with", "the", "overall", "survival", "as", "well", "as", "important", "clinico-pathological", "parameters", "showed", "that", "carriers", "of", "the", "T", "allele", "had", "a", "significantly", "less", "favourable", "course", "of", "the", "disease", "when", "compared", "to", "carriers", "of", "the", "homozygous", "CC", "genotype.", "In", "multivariate", "analysis", "the", "homozygous", "TT", "genotype", "was", "independently", "associated", "with", "a", "decreased", "overall", "survival.", "Our", "results", "suggest", "that", "the", "GNAS1", "T393C", "T393C", "T393C", " ", "polymorphism", "in", "the", "gene", "GNAS1", "of", "G", "protein", "is", "associated", "with", "survival", "of", "patients", "with", "invasive", "breast", "carcinoma." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The GNAS1 locus encodes the G(alpha)s protein which stimulates the formation of cyclic AMP (cAMP). Subsequently the cAMP pathway mediates various pleiotropic effects including regulation of apoptosis and proliferation. We have recently shown that genotypes of the single nucleotide polymorphism (SNP) T393C SNP ) T393C in the gene GNAS1 are associated with survival of patients suffering from bladder, renal cell and colorectal carcinoma. In the present study, the genotypes of the T393C SNP were determined in 279 patients with invasive breast carcinoma. Comparing the genotypes with the overall survival as well as important clinico-pathological parameters showed that carriers of the T allele had a significantly less favourable course of the disease when compared to carriers of the homozygous CC genotype. In multivariate analysis the homozygous TT genotype was independently associated with a decreased overall survival. Our results suggest that the GNAS1 T393C T393C T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma.
[ 2, 1920, 9005, 26456, 6730, 9937, 1920, 49, 12, 4595, 13, 61, 2213, 2154, 11803, 1920, 3337, 1927, 9821, 3681, 12, 6225, 13, 18, 5326, 1920, 6225, 3374, 10412, 3425, 20233, 2564, 2710, 3640, 1927, 4091, 1930, 4031, 18, 2038, 2162, 3998, 2522, 1988, 7059, 1927, 1920, 2957, 5489, 8218, 12, 6821, 13, 9627, 11436, 1030, 6821, 13, 9627, 11436, 1030, 1922, 1920, 2359, 9005, 26456, 2032, 2458, 1956, 3298, 1927, 2132, 11364, 2037, 7821, 16, 4604, 2024, 1930, 7820, 5373, 18, 1922, 1920, 2481, 2161, 16, 1920, 7059, 1927, 1920, 9627, 11436, 1030, 6821, 1985, 3180, 1922, 22227, 2132, 1956, 6044, 3739, 5373, 18, 5640, 1920, 7059, 1956, 1920, 3399, 3298, 1966, 2486, 1966, 2715, 6248, 1037, 17, 6598, 3673, 2594, 1988, 8974, 1927, 1920, 62, 5465, 2430, 43, 2567, 2941, 18845, 4914, 1927, 1920, 2573, 2469, 2452, 1942, 8974, 1927, 1920, 9419, 4928, 5619, 18, 1922, 6884, 2333, 1920, 9419, 7382, 5619, 1982, 6407, 2458, 1956, 43, 3261, 3399, 3298, 18, 2342, 2274, 3220, 1988, 1920, 9005, 26456, 9627, 11436, 1030, 9627, 11436, 1030, 9627, 11436, 1030, 8218, 1922, 1920, 2359, 9005, 26456, 1927, 49, 2213, 1977, 2458, 1956, 3298, 1927, 2132, 1956, 6044, 3739, 5373, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 3, 4, 4, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 3, 4, 4, 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
22810479
[ ":", "The", "effect", "of", "K-ras", "gene", "mutations", "on", "the", "overall", "survival", "was", "measured", "by", "the", "HR", "and", "95%", "CIs." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
: The effect of K-ras gene mutations on the overall survival was measured by the HR and 95% CIs.
[ 2, 30, 1920, 2495, 1927, 53, 17, 6520, 2359, 3527, 1990, 1920, 3399, 3298, 1982, 3045, 2007, 1920, 3668, 1930, 3002, 9, 5848, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
26925673
[ "##", "MATERIALS", "AND", "METHODS" ]
[ 0, 0, 0, 0 ]
## MATERIALS AND METHODS
[ 2, 7, 7, 4751, 1930, 2860, 3 ]
[ 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, -100 ]
12534642
[ "From", "genomic", "DNA,", "114", "British", "Caucasians", "(49", "colorectal", "cancer", "cases", "and", "65", "controls)", "were", "genotyped", "for", "the", "CYP1A2", "polymorphisms", "-3858G-->A", "(allele", "CYP1A2*1C),", "-2464T-->delT", "(CYP1A2*1D),", "-740T-->G", "(CYP1A2*1E", "and", "*1G),", "-164A-->C", "(CYP1A2*1F),", "63C-->G", "(CYP1A2*2),", "and", "1545T-->C", "(alleles", "CYP1A2*1B,", "*1G,", "*1H", "and", "*3),", "using", "polymerase", "chain", "reaction-restriction", "fragment", "length", "polymorphism", "assays.", "All", "patients", "and", "controls", "were", "phenotyped", "for", "CYP1A2", "by", "h.p.l.c.", "analysis", "of", "urinary", "caffeine", "metabolites." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
From genomic DNA, 114 British Caucasians (49 colorectal cancer cases and 65 controls) were genotyped for the CYP1A2 polymorphisms -3858G-->A (allele CYP1A2*1C), -2464T-->delT (CYP1A2*1D), -740T-->G (CYP1A2*1E and *1G), -164A-->C (CYP1A2*1F), 63C-->G (CYP1A2*2), and 1545T-->C (alleles CYP1A2*1B, *1G, *1H and *3), using polymerase chain reaction-restriction fragment length polymorphism assays. All patients and controls were phenotyped for CYP1A2 by h.p.l.c. analysis of urinary caffeine metabolites.
[ 2, 2037, 4935, 2678, 16, 11296, 14885, 21338, 12, 4343, 7820, 2539, 2919, 1930, 4459, 3562, 13, 1985, 14401, 1958, 1920, 6120, 23750, 8321, 17, 25800, 1025, 1029, 17, 17, 34, 43, 12, 5465, 6120, 23750, 14, 6853, 13, 16, 17, 21141, 1006, 1031, 17, 17, 34, 17496, 12, 6120, 23750, 14, 8046, 13, 16, 17, 5446, 1008, 1031, 17, 17, 34, 49, 12, 6120, 23750, 14, 10720, 1930, 14, 15957, 13, 16, 17, 15170, 1019, 17, 17, 34, 45, 12, 6120, 23750, 14, 14078, 13, 16, 4968, 1030, 17, 17, 34, 49, 12, 6120, 23750, 14, 22, 13, 16, 1930, 14396, 1015, 1031, 17, 17, 34, 45, 12, 7096, 6120, 23750, 14, 5462, 16, 14, 15957, 16, 14, 5189, 1930, 14, 23, 13, 16, 2193, 6479, 4659, 3227, 17, 7587, 5302, 3471, 8218, 4614, 18, 2136, 2132, 1930, 3562, 1985, 4629, 1007, 1958, 6120, 23750, 2007, 50, 18, 58, 18, 54, 18, 45, 18, 2333, 1927, 7075, 14119, 6926, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9731891
[ "In", "the", "125", "cases", "studied,", "there", "were", "53", "tumors", "with", "mutations", "of", "the", "p53", "gene.", "p53", "mutations", "correlated", "with", "lymph", "node", "metastases", "from", "right", "colon", "carcinoma", "cases", "(61%),", "and", "all", "cases", "with", "p53", "mutations", "and", "microsatellite", "instability", "were", "AJCC/UICC", "Stage", "III", "(Dukes", "Stage", "C).", "In", "the", "right", "colon", "carcinoma", "cases", "the", "rate", "of", "microsatellite", "instability", "was", "related", "to", "the", "tumor", "size", "(19%", "in", "tumors", "measuring", "<", "4", "cm,", "and", "34%", "in", "tumors", "measuring", ">", "4", "cm).", "No", "correlation", "between", "microsatellite", "instability", "and", "p53", "mutations", "was", "detected.", "In", "the", "left", "colon", "carcinoma", "cases,", "p53", "mutations", "were", "detected", "in", "41%", "of", "tumors", "and", "microsatellite", "instability", "in", "14%;", "neither", "finding", "was", "related", "to", "the", "tumor", "size.", "Mutations", "of", "the", "hMLH1", "and", "hMSH2", "mismatch", "repair", "genes", "were", "detected", "in", "7", "of", "24", "cases", "with", "marked", "microsatellite", "instability." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability and p53 mutations was detected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither finding was related to the tumor size. Mutations of the hMLH1 and hMSH2 mismatch repair genes were detected in 7 of 24 cases with marked microsatellite instability.
[ 2, 1922, 1920, 7151, 2919, 3942, 16, 2276, 1985, 4522, 3861, 1956, 3527, 1927, 1920, 5105, 2359, 18, 5105, 3527, 4374, 1956, 3541, 6267, 8174, 2037, 3659, 4120, 5373, 2919, 12, 5473, 9, 13, 16, 1930, 2136, 2919, 1956, 5105, 3527, 1930, 16069, 9557, 1985, 13937, 2437, 19, 20487, 2437, 3587, 4337, 12, 26101, 1036, 3587, 45, 13, 18, 1922, 1920, 3659, 4120, 5373, 2919, 1920, 2769, 1927, 16069, 9557, 1982, 2712, 1942, 1920, 2798, 3081, 12, 2282, 9, 1922, 3861, 6711, 32, 24, 3195, 16, 1930, 3540, 9, 1922, 3861, 6711, 34, 24, 3195, 13, 18, 2239, 3670, 2192, 16069, 9557, 1930, 5105, 3527, 1982, 3330, 18, 1922, 1920, 3506, 4120, 5373, 2919, 16, 5105, 3527, 1985, 3330, 1922, 4353, 9, 1927, 3861, 1930, 16069, 9557, 1922, 2607, 9, 31, 7132, 2849, 1982, 2712, 1942, 1920, 2798, 3081, 18, 3527, 1927, 1920, 5833, 1024, 8600, 1930, 21904, 6951, 10265, 5059, 2628, 1985, 3330, 1922, 27, 1927, 2686, 2919, 1956, 4961, 16069, 9557, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
8431846
[ "The", "authors", "report", "the", "case", "of", "a", "48-year-old", "woman", "with", "rectal", "cancer", "accompanied", "by", "multiple", "polyps", "in", "the", "esophagus,", "stomach,", "and", "colorectum.", "Histologically,", "the", "polypoid", "lesions", "in", "the", "esophagus,", "stomach,", "and", "colorectum", "showed", "a", "thickened", "mucosa,", "hyperplastic", "polyps,", "and", "mixed", "hyperplastic", "adenomatous", "polyps,", "respectively.", "Karyotype", "analysis", "showed", "46,", "xx,", "inv(3)(p12.2q25.3)", "in", "all", "20", "inspected", "peripheral", "lymphocytes.", "By", "Southern", "blot", "with", "a", "c-raf", "probe,", "one", "allele", "of", "the", "c-raf-1", "gene,", "which", "has", "been", "mapped", "on", "chromosome", "3p25,", "was", "deleted", "from", "the", "rearranged", "c-raf", " ", "probe,", "one", "allele", "of", "the", "c-raf-1", "gene,", "which", "has", "been", "mapped", "on", "chromosome", "3p25,", "was", "deleted", "from", "the", "rearranged", "chromosome", "3", "in", "the", "peripheral", "lymphocytes,", "intact", "colonic", "mucosa,", "and", "cancer", "tissue." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
The authors report the case of a 48-year-old woman with rectal cancer accompanied by multiple polyps in the esophagus, stomach, and colorectum. Histologically, the polypoid lesions in the esophagus, stomach, and colorectum showed a thickened mucosa, hyperplastic polyps, and mixed hyperplastic adenomatous polyps, respectively. Karyotype analysis showed 46, xx, inv(3)(p12.2q25.3) in all 20 inspected peripheral lymphocytes. By Southern blot with a c-raf probe, one allele of the c-raf-1 gene, which has been mapped on chromosome 3p25, was deleted from the rearranged c-raf probe, one allele of the c-raf-1 gene, which has been mapped on chromosome 3p25, was deleted from the rearranged chromosome 3 in the peripheral lymphocytes, intact colonic mucosa, and cancer tissue.
[ 2, 1920, 3875, 3809, 1920, 3087, 1927, 43, 3427, 17, 2476, 17, 4156, 10440, 1956, 11635, 2539, 7936, 2007, 3137, 17410, 1922, 1920, 16749, 16, 11399, 16, 1930, 4677, 2089, 1989, 18, 15055, 16, 1920, 6240, 2642, 4518, 1922, 1920, 16749, 16, 11399, 16, 1930, 4677, 2089, 1989, 2594, 43, 25981, 9680, 16, 28733, 17410, 16, 1930, 4985, 28733, 30390, 17410, 16, 2763, 18, 21954, 2333, 2594, 4182, 16, 22995, 16, 2269, 12, 23, 13, 12, 28443, 18, 22, 23470, 1015, 18, 23, 13, 1922, 2136, 2036, 23396, 5009, 7257, 18, 2007, 9257, 4918, 1956, 43, 45, 17, 12783, 5598, 16, 2340, 5465, 1927, 1920, 45, 17, 12783, 17, 21, 2359, 16, 2154, 2258, 2252, 9225, 1990, 5597, 11469, 4198, 16, 1982, 11782, 2037, 1920, 26669, 45, 17, 12783, 5598, 16, 2340, 5465, 1927, 1920, 45, 17, 12783, 17, 21, 2359, 16, 2154, 2258, 2252, 9225, 1990, 5597, 11469, 4198, 16, 1982, 11782, 2037, 1920, 26669, 5597, 23, 1922, 1920, 5009, 7257, 16, 6718, 12401, 9680, 16, 1930, 2539, 2960, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9841584
[ "Carriers", "of", "a", "mutation", " ", "for", "hereditary", "nonpolyposis", "colorectal", "cancer", "who", "were", "25", "years", "of", "age." ]
[ 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Carriers of a mutation for hereditary nonpolyposis colorectal cancer who were 25 years of age.
[ 2, 8974, 1927, 43, 3979, 1958, 16321, 24857, 26558, 2420, 1937, 7820, 2539, 2746, 1985, 2637, 2739, 1927, 2632, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9731891
[ "Left", "and", "right", "colon", "carcinomas", "can", "display", "different", "clinical,", "pathologic,", "and", "genetic", "characteristics.", "The", "purpose", "of", "this", "study", "was", "to", "characterize", "multiple", "molecular", "genetic", "alterations", "in", "sporadic", "colon", "carcinoma", "and", "to", "correlate", "them", "with", "the", "location", "of", "the", "tumors", "and", "with", "lymph", "node", "metastasis." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis.
[ 2, 3506, 1930, 3659, 4120, 10691, 2112, 4434, 2413, 2535, 16, 11896, 16, 1930, 3299, 3779, 18, 1920, 5120, 1927, 2052, 2161, 1982, 1942, 8063, 3137, 3272, 3299, 5996, 1922, 13088, 4120, 5373, 1930, 1942, 8474, 3581, 1956, 1920, 5185, 1927, 1920, 3861, 1930, 1956, 3541, 6267, 5967, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
19276868
[ "A", "lead", "molecule,", "UA62784,", "was", "identified", "to", "be", "selectively", "cytotoxic", "against", "cancer", "cells", "with", "deficient", "DPC4.", "UA62784", "preferentially", "induces", "cell", "cycle", "arrest", "and", "apoptosis", "in", "cells", "with", "deficient", "DPC4.", "It", "also", "selectively", "reduces", "the", "clonogenicity", "of", "DPC4-deficient", "cells", "on", "soft", "agar", "when", "compared", "with", "cells", "with", "wild", "type", "DPC4.", "We", "further", "demonstrate", "that", "UA62784", "induces", "CDC2", "kinase", "activity", "preferentially", "in", "DPC4-negative", "cells." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
A lead molecule, UA62784, was identified to be selectively cytotoxic against cancer cells with deficient DPC4. UA62784 preferentially induces cell cycle arrest and apoptosis in cells with deficient DPC4. It also selectively reduces the clonogenicity of DPC4-deficient cells on soft agar when compared with cells with wild type DPC4. We further demonstrate that UA62784 induces CDC2 kinase activity preferentially in DPC4-negative cells.
[ 2, 43, 2949, 5388, 16, 17942, 8166, 7950, 1006, 16, 1982, 2899, 1942, 1998, 9331, 8377, 3316, 2539, 2094, 1956, 5778, 25488, 1006, 18, 17942, 8166, 7950, 1006, 10662, 6387, 2024, 4048, 8048, 1930, 4091, 1922, 2094, 1956, 5778, 25488, 1006, 18, 2176, 2222, 9331, 7268, 1920, 25494, 1999, 1927, 25488, 1006, 17, 5778, 2094, 1990, 3793, 8963, 2469, 2452, 1956, 2094, 1956, 3576, 2601, 25488, 1006, 18, 2038, 2520, 4504, 1988, 17942, 8166, 7950, 1006, 6387, 28190, 4016, 2455, 10662, 1922, 25488, 1006, 17, 3136, 2094, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
3399825
[ "One", "hundred", "and", "seventy-six", "individuals", "with", "various", "colorectal", "diseases", "were", "investigated", "simultaneously", "for", "increased", "in", "vitro", "tetraploidy", "in", "dermal", "fibroblast", "cultures", "and", "for", "occult", "mandibular", "osteomas.", "In", "only", "10", "of", "the", "176", "persons", "were", "both", "presumed", "markers", "of", "colorectal", "genetic", "predisposition", "present", "in", "the", "same", "individual.", "No", "evidence", "was", "found", "that", "these", "traits", "are", "causally", "associated.", "A", "combination", "of", "the", "two", "presumed", "markers", "showed", "a", "tendency", "towards", "occurrence", "in", "individuals", "with", "a", "positive", "family", "history", "of", "colorectal", "cancer", "among", "first-degree", "relatives." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
One hundred and seventy-six individuals with various colorectal diseases were investigated simultaneously for increased in vitro tetraploidy in dermal fibroblast cultures and for occult mandibular osteomas. In only 10 of the 176 persons were both presumed markers of colorectal genetic predisposition present in the same individual. No evidence was found that these traits are causally associated. A combination of the two presumed markers showed a tendency towards occurrence in individuals with a positive family history of colorectal cancer among first-degree relatives.
[ 2, 2340, 8295, 1930, 16270, 17, 3798, 3445, 1956, 3425, 7820, 3902, 1985, 3845, 7159, 1958, 2502, 1922, 3596, 29389, 1012, 1922, 14230, 10541, 5054, 1930, 1958, 23065, 14951, 4416, 4956, 18, 1922, 2444, 2119, 1927, 1920, 15797, 7618, 1985, 2321, 15326, 4432, 1927, 7820, 3299, 17757, 2481, 1922, 1920, 2841, 2725, 18, 2239, 3095, 1982, 2435, 1988, 2144, 7226, 2032, 9263, 1954, 2458, 18, 43, 3921, 1927, 1920, 2288, 15326, 4432, 2594, 43, 10080, 5681, 6564, 1922, 3445, 1956, 43, 2843, 3416, 4403, 1927, 7820, 2539, 2706, 2561, 17, 4647, 12280, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
20196079
[ "Oncogenic", "KRAS", "is", "not", "necessary", "for", "Wnt", "signalling", "activation", "in", "APC-associated", "FAP", "adenomas." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Oncogenic KRAS is not necessary for Wnt signalling activation in APC-associated FAP adenomas.
[ 2, 11446, 11083, 1977, 2084, 4680, 1958, 7028, 8076, 2936, 1922, 9187, 17, 2458, 20592, 16787, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9439149
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
[ 2, 7, 7, 2860, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
8709782
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
23012243
[ "Lynch", "syndrome", "is", "characterized", "by", "mutations", "in", "one", "of", "four", "mismatch", "repair", "genes,", "MLH1,", "MSH2,", "MSH6,", "or", "PMS2.", "Clinical", "mutation", "analysis", "of", "these", "genes", "includes", "sequencing", "of", "exonic", "regions", "and", "deletion/duplication", "analysis.", "However,", "detection", "of", "deletions", "and", "duplications", "in", "PMS2", "has", "previously", "been", "confined", "to", "Exons", "1-11", "due", "to", "gene", "conversion", "between", "PMS2", "and", "the", "pseudogene", "PMS2CL", "in", "the", "remaining", "3'", "exons", "(Exons", "12-15).", "We", "have", "recently", "described", "an", "MLPA-based", "method", "that", "permits", "detection", "of", "deletions", "of", "PMS2", "Exons", "12-15;", "however,", "the", "frequency", "of", "such", "deletions", "has", "not", "yet", "been", "determined.", "To", "address", "this", "question,", "we", "tested", "for", "3'", "deletions", "in", "58", "samples", "that", "were", "reported", "to", "be", "negative", "for", "PMS2", "mutations", "using", "previously", "available", "methods.", "All", "samples", "were", "from", "individuals", "whose", "tumors", "exhibited", "loss", "of", "PMS2", "immunohistochemical", "staining", "without", "concomitant", "loss", "of", "MLH1", "immunostaining.", "We", "identified", "seven", "samples", "in", "this", "cohort", "with", "deletions", "in", "the", "3'", "region", "of", "PMS2,", "including", "three", "previously", "reported", "samples", "with", "deletions", "of", "Exons", "13-15", "(two", "samples)", "and", "Exons", "14-15.", "Also", "detected", "were", "deletions", "of", "Exons", "12-15,", "Exon", "13,", "and", "Exon", "14", "(two", "samples).", "Breakpoint", "analysis", "of", "the", "intragenic", "deletions", "suggests", "they", "occurred", "through", "Alu-mediated", "recombination.", "Our", "results", "indicate", "that", "∼12%", "of", "samples", "suspected", "of", "harboring", "a", "PMS2", "3'", "Exons", " ", "of", "the", "PMS2", "gene." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 7, 8, 0, 0, 0, 0, 0 ]
Lynch syndrome is characterized by mutations in one of four mismatch repair genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in PMS2 has previously been confined to Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method that permits detection of deletions of PMS2 Exons 12-15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3' deletions in 58 samples that were reported to be negative for PMS2 mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3' region of PMS2, including three previously reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15. Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through Alu-mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a PMS2 3' Exons of the PMS2 gene.
[ 2, 27452, 4741, 1977, 4378, 2007, 3527, 1922, 2340, 1927, 3006, 10265, 5059, 2628, 16, 25265, 16, 26693, 16, 19864, 1016, 16, 2014, 13673, 1028, 18, 2535, 3979, 2333, 1927, 2144, 2628, 5921, 4754, 1927, 29070, 3451, 1930, 5541, 19, 12630, 2333, 18, 2406, 16, 3805, 1927, 10550, 1930, 20559, 1922, 13673, 1028, 2258, 3024, 2252, 13184, 1942, 10419, 21, 17, 2513, 2810, 1942, 2359, 7309, 2192, 13673, 1028, 1930, 1920, 11520, 14687, 13673, 10866, 1024, 1922, 1920, 5719, 23, 11, 10419, 12, 10419, 2369, 17, 2461, 13, 18, 2038, 2162, 3998, 2910, 1925, 2646, 4302, 17, 2454, 2417, 1988, 16299, 3805, 1927, 10550, 1927, 13673, 1028, 10419, 2369, 17, 2461, 31, 2406, 16, 1920, 3528, 1927, 2427, 10550, 2258, 2084, 4898, 2252, 3180, 18, 1942, 4640, 2052, 3863, 16, 2038, 3620, 1958, 23, 11, 10550, 1922, 4804, 2785, 1988, 1985, 2568, 1942, 1998, 3136, 1958, 13673, 1028, 3527, 2193, 3024, 3322, 2860, 18, 2136, 2785, 1985, 2037, 3445, 6098, 3861, 5065, 3257, 1927, 13673, 1028, 9885, 4166, 2979, 8537, 3257, 1927, 25265, 10930, 18, 2038, 2899, 5260, 2785, 1922, 2052, 4382, 1956, 10550, 1922, 1920, 23, 11, 3031, 1927, 13673, 1028, 16, 2710, 2559, 3024, 2568, 2785, 1956, 10550, 1927, 10419, 2590, 17, 2461, 12, 2288, 2785, 13, 1930, 10419, 2607, 17, 2461, 18, 2222, 3330, 1985, 10550, 1927, 10419, 2369, 17, 2461, 16, 7049, 2590, 16, 1930, 7049, 2607, 12, 2288, 2785, 13, 18, 24698, 2333, 1927, 1920, 27911, 7245, 10550, 4015, 2611, 4807, 2596, 24664, 17, 3434, 7827, 18, 2342, 2274, 3579, 1988, 21174, 1028, 9, 1927, 2785, 9407, 1927, 12827, 43, 13673, 1028, 23, 11, 10419, 1927, 1920, 13673, 1028, 2359, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 7, 8, 8, 0, 0, 0, 0, 0, 0, -100 ]
9731891
[ "Left", "and", "right", "colon", "carcinomas", "can", "display", "different", "clinical,", "pathologic,", "and", "genetic", "characteristics.", "The", "purpose", "of", "this", "study", "was", "to", "characterize", "multiple", "molecular", "genetic", "alterations", "in", "sporadic", "colon", "carcinoma", "and", "to", "correlate", "them", "with", "the", "location", "of", "the", "tumors", "and", "with", "lymph", "node", "metastasis." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis.
[ 2, 3506, 1930, 3659, 4120, 10691, 2112, 4434, 2413, 2535, 16, 11896, 16, 1930, 3299, 3779, 18, 1920, 5120, 1927, 2052, 2161, 1982, 1942, 8063, 3137, 3272, 3299, 5996, 1922, 13088, 4120, 5373, 1930, 1942, 8474, 3581, 1956, 1920, 5185, 1927, 1920, 3861, 1930, 1956, 3541, 6267, 5967, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14645426
[ "In", "five", "of", "22", "patients", "with", "a", "positive", "first-degree", "family", "history", "for", "hereditary", "nonpolyposis", "colorectal", "cancer", "(HNPCC)-related", "cancers,", "pathogenic", "germline", "mutations", "were", "found", "(one", "MLH1,", "three", "MSH2,", "and", "one", "MSH6).", "Four", "mutation", "carriers", "belonged", "to", "families", "fulfilling", "the", "revised", "Amsterdam", "criteria.", "No", "mutations", "were", "found", "in", "the", "35", "patients", "without", "such", "family", "history", "(P", "=.006).", "MSI", "was", "detected", "in", "20", "of", "57", "cancers,", "among", "which", "four", "were", "from", "mutation", "carriers.", "In", "23", "of", "51", "cancers,", "one", "or", "more", "MMR", "protein", "was", "absent;", "in", "all", "five", "mutation", "carriers,", "immunostaining", "indicated", "the", "involved", "MMR", "gene." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
In five of 22 patients with a positive first-degree family history for hereditary nonpolyposis colorectal cancer (HNPCC)-related cancers, pathogenic germline mutations were found (one MLH1, three MSH2, and one MSH6). Four mutation carriers belonged to families fulfilling the revised Amsterdam criteria. No mutations were found in the 35 patients without such family history (P =.006). MSI was detected in 20 of 57 cancers, among which four were from mutation carriers. In 23 of 51 cancers, one or more MMR protein was absent; in all five mutation carriers, immunostaining indicated the involved MMR gene.
[ 2, 1922, 3628, 1927, 2950, 2132, 1956, 43, 2843, 2561, 17, 4647, 3416, 4403, 1958, 16321, 24857, 26558, 2420, 1937, 7820, 2539, 12, 9888, 7693, 1030, 13, 17, 2712, 5717, 16, 8070, 12237, 3527, 1985, 2435, 12, 2340, 25265, 16, 2559, 26693, 16, 1930, 2340, 19864, 1016, 13, 18, 3006, 3979, 8974, 18293, 1942, 5767, 28606, 1920, 10041, 27002, 4164, 18, 2239, 3527, 1985, 2435, 1922, 1920, 3259, 2132, 2979, 2427, 3416, 4403, 12, 58, 33, 18, 12791, 13, 18, 17355, 1982, 3330, 1922, 2036, 1927, 4786, 5717, 16, 2706, 2154, 3006, 1985, 2037, 3979, 8974, 18, 1922, 3020, 1927, 4892, 5717, 16, 2340, 2014, 2253, 16744, 2213, 1982, 7685, 31, 1922, 2136, 3628, 3979, 8974, 16, 10930, 3391, 1920, 3286, 16744, 2359, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
14734469
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
[ 2, 7, 7, 4355, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
20646601
[ "[Significance", "of", "K-ras", "detection", "in", "colorectal", "cancer].", "\n\n\n", "##", "OBJECTIVE" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[Significance of K-ras detection in colorectal cancer]. ## OBJECTIVE
[ 2, 37, 4550, 1927, 53, 17, 6520, 3805, 1922, 7820, 2539, 39, 18, 7, 7, 4470, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9841584
[ "Immediate", "prophylactic", "colectomy;", "delayed", "colectomy", "on", "the", "basis", "of", "age,", "adenoma,", "or", "diagnosis", "of", "colorectal", "cancer;", "and", "endoscopic", "surveillance.", "Prophylactic", "surgical", "options", "were", "proctocolectomy", "with", "ileoanal", "anastomosis", "and", "subtotal", "colectomy", "with", "ileorectal", "anastomosis." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Immediate prophylactic colectomy; delayed colectomy on the basis of age, adenoma, or diagnosis of colorectal cancer; and endoscopic surveillance. Prophylactic surgical options were proctocolectomy with ileoanal anastomosis and subtotal colectomy with ileorectal anastomosis.
[ 2, 8426, 14847, 21481, 2341, 3542, 31, 7083, 21481, 2341, 3542, 1990, 1920, 4859, 1927, 2632, 16, 16530, 16, 2014, 3574, 1927, 7820, 2539, 31, 1930, 10448, 7889, 18, 14847, 4548, 8416, 1985, 9823, 4575, 4879, 25419, 4575, 14930, 1956, 9940, 6952, 3163, 17331, 1930, 13329, 10868, 21481, 2341, 3542, 1956, 9940, 28834, 17331, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
12534642
[ "In", "114", "samples,", "the", "most", "frequent", "CYP1A2", "SNPs", "were", "1545T-->C", "(38.2%", "of", "tested", "chromosomes),", "-164A-->C", "(CYP1A2*1F,", "33.3%)", "and", "-2464T-->delT", "(CYP1A2*1D,", "4.82%).", "The", "SNPs", "were", "in", "linkage", "disequilibrium:", "the", "most", "frequent", "constellations", "were", "found", "to", "be", "-3858G/-2464T/-740T/-164A/63C/1545T", "(61.8%),", "-3858G/-2464T/-740T/-164C/63C/1545C", "(33.3%),", "and", "-3858G/-2464delT/-740T/-164A/63C/1545C", "(3.51%),", "with", "no", "significant", "frequency", "differences", "between", "cases", "and", "controls.", "In", "the", "phenotype", "analysis,", "lower", "caffeine", "metabolic", "ratios", "were", "detected", "in", "cases", "than", "in", "controls.", "This", "was", "significant", "in", "smokers", "(n", "=", "14,", "P", "=", "0.020),", "and", "in", "a", "subgroup", "of", "15", "matched", "case-control", "pairs", "(P", "=", "0.007),", "but", "it", "was", "not", "significant", "in", "nonsmokers", "(n", "=", "100,", "P", "=", "0.39).", "There", "was", "no", "detectable", "association", "between", "CYP1A2", "genotype", "and", "caffeine", "phenotype." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
In 114 samples, the most frequent CYP1A2 SNPs were 1545T-->C (38.2% of tested chromosomes), -164A-->C (CYP1A2*1F, 33.3%) and -2464T-->delT (CYP1A2*1D, 4.82%). The SNPs were in linkage disequilibrium: the most frequent constellations were found to be -3858G/-2464T/-740T/-164A/63C/1545T (61.8%), -3858G/-2464T/-740T/-164C/63C/1545C (33.3%), and -3858G/-2464delT/-740T/-164A/63C/1545C (3.51%), with no significant frequency differences between cases and controls. In the phenotype analysis, lower caffeine metabolic ratios were detected in cases than in controls. This was significant in smokers (n = 14, P = 0.020), and in a subgroup of 15 matched case-control pairs (P = 0.007), but it was not significant in nonsmokers (n = 100, P = 0.39). There was no detectable association between CYP1A2 genotype and caffeine phenotype.
[ 2, 1922, 11296, 2785, 16, 1920, 2501, 6439, 6120, 23750, 6084, 1985, 14396, 1015, 1031, 17, 17, 34, 45, 12, 3738, 18, 22, 9, 1927, 3620, 8597, 13, 16, 17, 15170, 1019, 17, 17, 34, 45, 12, 6120, 23750, 14, 14078, 16, 3401, 18, 23, 9, 13, 1930, 17, 21141, 1006, 1031, 17, 17, 34, 17496, 12, 6120, 23750, 14, 8046, 16, 24, 18, 6175, 9, 13, 18, 1920, 6084, 1985, 1922, 8611, 19264, 30, 1920, 2501, 6439, 4713, 30439, 1036, 1985, 2435, 1942, 1998, 17, 25800, 1025, 1029, 19, 17, 21141, 1006, 1031, 19, 17, 5446, 1008, 1031, 19, 17, 15170, 1019, 19, 4968, 1030, 19, 14396, 1015, 1031, 12, 5473, 18, 28, 9, 13, 16, 17, 25800, 1025, 1029, 19, 17, 21141, 1006, 1031, 19, 17, 5446, 1008, 1031, 19, 17, 15170, 1030, 19, 4968, 1030, 19, 14396, 20118, 12, 3401, 18, 23, 9, 13, 16, 1930, 17, 25800, 1025, 1029, 19, 17, 21141, 28660, 9551, 19, 17, 5446, 1008, 1031, 19, 17, 15170, 1019, 19, 4968, 1030, 19, 14396, 20118, 12, 23, 18, 4892, 9, 13, 16, 1956, 2239, 2228, 3528, 2886, 2192, 2919, 1930, 3562, 18, 1922, 1920, 4629, 2333, 16, 2826, 14119, 4487, 5835, 1985, 3330, 1922, 2919, 2254, 1922, 3562, 18, 2052, 1982, 2228, 1922, 8112, 12, 56, 33, 2607, 16, 58, 33, 20, 18, 18773, 13, 16, 1930, 1922, 43, 6200, 1927, 2461, 5992, 3087, 17, 2285, 5803, 12, 58, 33, 20, 18, 13298, 13, 16, 2308, 2176, 1982, 2084, 2228, 1922, 28500, 12, 56, 33, 2813, 16, 58, 33, 20, 18, 3886, 13, 18, 2276, 1982, 2239, 7398, 3279, 2192, 6120, 23750, 5619, 1930, 14119, 4629, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
26925673
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
26925673
[ "Cellular", "proliferation,", "morphology", "and", "cell", "cycle", "analysis", "were", "carried", "out", "in", "addition", "to", "Western", "blotting", "for", "detecting", "total", "Akt", "and", "p-Akt", "(at", "Thr308", "and", "Ser473)", "in", "the", "presence", "and", "absence", "of", "different", "concentrations", "of", "EA.", "Cell", "proliferation", "was", "also", "assessed", "in", "cells", "transfected", "with", "different", "concentrations", "of", "K-Ras", "siRNA", "or", "incubated", "with", "ellagic", "acid", "following", "transfection." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of K-Ras siRNA or incubated with ellagic acid following transfection.
[ 2, 3689, 4031, 16, 6076, 1930, 2024, 4048, 2333, 1985, 4371, 2397, 1922, 2459, 1942, 4540, 8390, 1958, 9227, 2698, 5496, 1930, 58, 17, 5496, 12, 2019, 8481, 22661, 1930, 2375, 20939, 13, 1922, 1920, 2990, 1930, 3905, 1927, 2413, 3295, 1927, 11377, 18, 2024, 4031, 1982, 2222, 3683, 1922, 2094, 5176, 1956, 2413, 3295, 1927, 53, 17, 6520, 5929, 2014, 3984, 1956, 20430, 12550, 2687, 2894, 6496, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
25029911
[ "These", "results", "demonstrate", "that", "Egr-1", "regulates", "NGX6", "gene", "transcription", "through", "an", "overlapping", "Sp1/Egr-1", "binding", "site", "as", "a", "positive", "regulator", "of", "NGX6", "gene." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
These results demonstrate that Egr-1 regulates NGX6 gene transcription through an overlapping Sp1/Egr-1 binding site as a positive regulator of NGX6 gene.
[ 2, 2144, 2274, 4504, 1988, 15850, 17, 21, 7014, 4375, 20649, 2359, 3213, 2596, 1925, 8984, 15847, 19, 15850, 17, 21, 2743, 3200, 1966, 43, 2843, 7888, 1927, 4375, 20649, 2359, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9841584
[ "Carriers", "of", "a", "mutation", "for", "hereditary", "nonpolyposis", "colorectal", "cancer", "who", "were", "25", "years", "of", "age." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Carriers of a mutation for hereditary nonpolyposis colorectal cancer who were 25 years of age.
[ 2, 8974, 1927, 43, 3979, 1958, 16321, 24857, 26558, 2420, 1937, 7820, 2539, 2746, 1985, 2637, 2739, 1927, 2632, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9439149
[ "Microsatellites", "are", "short", "repeated", "oligonucleotide", "sequences", "found", "throughout", "the", "human", "genome.", "High", "mutation", " ", "rates", "in", "microsatellite", "sequences", "have", "been", "found", "in", "tumors", "from", "patients", "with", "hereditary", "non-polyposis", "colorectal", "carcinoma", "and", "some", "sporadic", "carcinomas.", "However,", "little", "information", "is", "available", "regarding", "RER-positive", "phenotype", "in", "gastric", "carcinomas,", "particularly", "in", "terms", "of", "age", "of", "onset", "and", "other", "pathologic", "features,", "such", "as", "histologic", "types,", "degree", "of", "differentiation,", "location", "or", "stage", "of", "the", "carcinoma." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Microsatellites are short repeated oligonucleotide sequences found throughout the human genome. High mutation rates in microsatellite sequences have been found in tumors from patients with hereditary non-polyposis colorectal carcinoma and some sporadic carcinomas. However, little information is available regarding RER-positive phenotype in gastric carcinomas, particularly in terms of age of onset and other pathologic features, such as histologic types, degree of differentiation, location or stage of the carcinoma.
[ 2, 16069, 1036, 2032, 3662, 5116, 12346, 3709, 2435, 5264, 1920, 2616, 3843, 18, 2149, 3979, 3389, 1922, 16069, 3709, 2162, 2252, 2435, 1922, 3861, 2037, 2132, 1956, 16321, 2447, 17, 28641, 7820, 5373, 1930, 2673, 13088, 10691, 18, 2406, 16, 5082, 2988, 1977, 3322, 4667, 21325, 17, 2843, 4629, 1922, 6319, 10691, 16, 4443, 1922, 4430, 1927, 2632, 1927, 4727, 1930, 2303, 11896, 4075, 16, 2427, 1966, 12434, 3584, 16, 4647, 1927, 4155, 16, 5185, 2014, 3587, 1927, 1920, 5373, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
22615057
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
24225759
[ "To", "investigate", "the", "clinicopathologic", "and", "endoscopic", "features", "of", "precursor", "lesions", "associated", "with", "traditional", "serrated", "adenomas", "(TSAs)." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
To investigate the clinicopathologic and endoscopic features of precursor lesions associated with traditional serrated adenomas (TSAs).
[ 2, 1942, 4482, 1920, 26223, 1930, 10448, 4075, 1927, 7897, 4518, 2458, 1956, 6378, 20835, 1981, 16787, 12, 17309, 1036, 13, 18, 3 ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, -100 ]
9731891
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
[ 2, 7, 7, 4355, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]