id
stringlengths 7
8
| tokens
sequence | ner_tags
sequence | texts
stringlengths 0
8.69k
|
---|---|---|---|
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",
"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",
"fatty",
"acid",
"synthase",
"microsatellite",
"instability",
",",
"independent",
"of",
"CpG",
"island",
"methylator",
"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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
3,
4,
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 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 fatty acid synthase microsatellite instability , independent of CpG island methylator phenotype. |
24568449 | [] | [] | |
14645426 | [
"Endometrial",
"cancer",
"patients",
"(N",
"=",
"58),",
"who",
"were",
"diagnosed",
"at",
"less",
"than",
"50",
"years",
"of",
"age,",
"were",
"included",
"and",
"questioned",
"about",
"their",
"family",
"history.",
"Mutation",
"analysis",
"of",
"the",
"MLH1,",
"MSH2,",
"and",
"MSH6",
"genes",
"was",
"performed",
"(denaturing",
"gradient",
"gel",
"electrophoresis",
"and",
"sequence",
"analysis",
"to",
"detect",
"small",
"mutations",
"and",
"multiplex",
"ligation-dependent",
"probe",
"amplification",
"to",
"detect",
"large",
"deletions",
"or",
"duplications).",
"For",
"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,
0,
0,
0,
0,
0,
0
] | Endometrial cancer patients (N = 58), who were diagnosed at less than 50 years of age, were included and questioned about their family history. Mutation analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and multiplex ligation-dependent probe amplification to detect large deletions or duplications). For MSI analysis, five consensus markers were used, and immunostaining of the three MMR proteins was performed. |
8709782 | [
"We",
"evaluated",
"the",
"incidence",
"of",
"rectal",
"cancer",
"in",
"polyposis",
"patients",
"who",
"had",
"undergone",
"IRA,",
"and",
"examined",
"whether",
"the",
"requirement",
"for",
"subsequent",
"rectal",
"excision",
"because",
"of",
"cancer",
"or",
"uncontrollable",
"polyps",
"was",
"related",
"to",
"the",
"site",
"of",
"mutation."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 the incidence of rectal cancer in polyposis patients who had undergone IRA, and examined whether the requirement for subsequent rectal excision because of cancer or uncontrollable polyps was related to the site of mutation. |
22810479 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
22810479 | [
"##",
"DATA",
"SOURCES"
] | [
0,
0,
0
] | ## DATA SOURCES |
24225759 | [
"Traditional",
"serrated",
"adenoma",
"of",
"the",
"colorectum:",
"clinicopathologic",
"implications",
"and",
"endoscopic",
"findings",
"of",
"the",
"precursor",
"lesions.",
"\n\n\n",
"##",
"OBJECTIVES"
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Traditional serrated adenoma of the colorectum: clinicopathologic implications and endoscopic findings of the precursor lesions.
## OBJECTIVES |
17186357 | [
"The",
"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,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | The T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma. |
9841584 | [
"All",
"risk-reduction",
"strategies",
"led",
"to",
"large",
"gains",
"in",
"life",
"expectancy",
"for",
"carriers",
"of",
"a",
"mutation",
"for",
"hereditary",
"nonpolyposis",
"colorectal",
"cancer,",
"with",
"benefits",
"ranging",
"from",
"13.5",
"years",
"for",
"surveillance",
"to",
"15.6",
"years",
"for",
"prophylactic",
"proctocolectomy",
"at",
"25",
"years",
"of",
"age",
"compared",
"with",
"no",
"intervention.",
"The",
"benefits",
"of",
"colectomy",
"compared",
"with",
"surveillance",
"decreased",
"with",
"increasing",
"age",
"and",
"were",
"minimal",
"if",
"colectomy",
"was",
"performed",
"at",
"the",
"time",
"of",
"colorectal",
"cancer",
"diagnosis.",
"When",
"health-related",
"quality",
"of",
"life",
"was",
"considered,",
"surveillance",
"led",
"to",
"the",
"greatest",
"quality-adjusted",
"life",
"expectancy",
"benefit",
"(3.1",
"years",
"compared",
"with",
"proctocolectomy",
"and",
"0.3",
"years",
"compared",
"with",
"subtotal",
"colectomy)."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | All risk-reduction strategies led to large gains in life expectancy for carriers of a mutation for hereditary nonpolyposis colorectal cancer, with benefits ranging from 13.5 years for surveillance to 15.6 years for prophylactic proctocolectomy at 25 years of age compared with no intervention. The benefits of colectomy compared with surveillance decreased with increasing age and were minimal if colectomy was performed at the time of colorectal cancer diagnosis. When health-related quality of life was considered, surveillance led to the greatest quality-adjusted life expectancy benefit (3.1 years compared with proctocolectomy and 0.3 years compared with subtotal colectomy). |
20646601 | [
"##",
"CONCLUSION"
] | [
0,
0
] | ## CONCLUSION |
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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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. |
23132392 | [
"##",
"METHODS"
] | [
0,
0
] | ## METHODS |
9476377 | [
"##",
"METHODS",
"AND",
"RESULTS"
] | [
0,
0,
0,
0
] | ## METHODS AND RESULTS |
9731891 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
1347643 | [
"Carcinogenesis",
"is",
"a",
"multistage",
"process",
"that",
"has",
"been",
"characterized",
"both",
"by",
"the",
"activation",
"of",
"cellular",
"oncogenes",
"and",
"by",
"the",
"loss",
"of",
"function",
"of",
"tumor",
"suppressor",
"genes.",
"Colorectal",
"cancer",
"has",
"been",
"associated",
"with",
"the",
"activation",
"of",
"ras",
"oncogenes",
"and",
"with",
"the",
"deletion",
"of",
"multiple",
"chromosomal",
"regions",
"including",
"chromosomes",
"5q,",
"17p,",
"and",
"18q.",
"Such",
"chromosome",
"loss",
"is",
"often",
"suggestive",
"of",
"the",
"deletion",
"or",
"loss",
"of",
"function",
"of",
"tumor",
"suppressor",
"genes.",
"The",
"candidate",
"tumor",
"suppressor",
"genes",
"from",
"these",
"regions",
"are,",
"respectively,",
"MCC",
"and/or",
"APC,",
"p53,",
"and",
"DCC.",
"In",
"order",
"to",
"further",
"our",
"understanding",
"of",
"the",
"molecular",
"and",
"genetic",
"mechanisms",
"involved",
"in",
"tumor",
"progression",
"and,",
"thereby,",
"of",
"normal",
"cell",
"growth,",
"it",
"is",
"important",
"to",
"determine",
"whether",
"defects",
"in",
"one",
"or",
"more",
"of",
"these",
"loci",
"contribute",
"functionally",
"in",
"the",
"progression",
"to",
"malignancy",
"in",
"colorectal",
"cancer",
"and",
"whether",
"correction",
"of",
"any",
"of",
"these",
"defects",
"restores",
"normal",
"growth",
"control",
"in",
"vitro",
"and",
"in",
"vivo.",
"To",
"address",
"this",
"question,",
"we",
"have",
"utilized",
"the",
"technique",
"of",
"microcell-mediated",
"chromosome",
"transfer",
"to",
"introduce",
"normal",
"human",
"chromosomes",
"5,",
"17,",
"and",
"18",
"individually",
"into",
"recipient",
"colorectal",
"cancer",
"cells.",
"Additionally,",
"chromosome",
"15",
"was",
"introduced",
"into",
"SW480",
"cells",
"as",
"an",
"irrelevant",
"control",
"chromosome.",
"While",
"the",
"introduction",
"of",
"chromosome",
"17",
"chromosome",
"15",
"chromosomes",
"5q,",
"17p,",
"and",
"18q",
".",
"Such",
"chromosome",
"loss",
"is",
"often",
"suggestive",
"of",
"the",
"deletion",
"or",
"loss",
"of",
"function",
"of",
"tumor",
"suppressor",
"genes.",
"The",
"candidate",
"tumor",
"suppressor",
"genes",
"from",
"these",
"regions",
"are,",
"respectively,",
"MCC",
"and/or",
"APC,",
"p53,",
"and",
"DCC.",
"In",
"order",
"to",
"further",
"our",
"understanding",
"of",
"the",
"molecular",
"and",
"genetic",
"mechanisms",
"involved",
"in",
"tumor",
"progression",
"and,",
"thereby,",
"of",
"normal",
"cell",
"growth,",
"it",
"is",
"important",
"to",
"determine",
"whether",
"defects",
"in",
"one",
"or",
"more",
"of",
"these",
"loci",
"contribute",
"functionally",
"in",
"the",
"progression",
"to",
"malignancy",
"in",
"colorectal",
"cancer",
"and",
"whether",
"correction",
"of",
"any",
"of",
"these",
"defects",
"restores",
"normal",
"growth",
"control",
"in",
"vitro",
"and",
"in",
"vivo.",
"To",
"address",
"this",
"question,",
"we",
"have",
"utilized",
"the",
"technique",
"of",
"microcell-mediated",
"chromosome",
"transfer",
"to",
"introduce",
"normal",
"human",
"chromosomes",
"5,",
"17,",
"and",
"18",
"individually",
"into",
"recipient",
"colorectal",
"cancer",
"cells.",
"Additionally,",
"chromosome",
"15",
"was",
"introduced",
"into",
"SW480",
"cells",
"as",
"an",
"irrelevant",
"control",
"chromosome.",
"While",
"the",
"introduction",
"of",
"chromosome",
"17",
"into",
"the",
"tumorigenic",
"colorectal",
"cell",
"line",
"SW480",
"yielded",
"no",
"viable",
"clones,",
"cell",
"lines",
"were",
"established",
"after",
"the",
"introduction",
"of",
"chromosomes",
"15,",
"5,",
"and",
"18.",
"Hybrids",
"containing",
"chromosome",
"18",
"are",
"morphologically",
"similar",
"to",
"the",
"parental",
"line,",
"whereas",
"those",
"containing",
"chromosome",
"5",
"are",
"morphologically",
"distinct",
"from",
"the",
"parental",
"cell",
"line,",
"being",
"small,",
"polygonal,",
"and",
"tightly",
"packed.",
"SW480-chromosome",
"5",
"hybrids",
"are",
"strongly",
"suppressed",
"for",
"tumorigenicity,",
"while",
"SW480-chromosome",
"18",
"hybrids",
"produce",
"slowly",
"growing",
"tumors",
"in",
"some",
"of",
"the",
"animals",
"injected.",
"Hybrids",
"containing",
"the",
"introduced",
"chromosome",
"18",
"but",
"was",
"significantly",
"reduced",
"in",
"several",
"of",
"the",
"tumor",
"reconstitute",
"cell",
"lines.",
"Introduction",
"of",
"chromosome",
"5",
"had",
"little",
"to",
"no",
"effect",
"on",
"responsiveness,",
"whereas",
"transfer",
"ot",
"chromosome",
"18",
"restored",
"responsiveness",
"to",
"some",
"degree.",
"Our",
"findings",
"indicate",
"that",
"while",
"multiple",
"defects",
"in",
"tumor",
"suppressor",
"genes",
"seem",
"to",
"be",
"required",
"for",
"progression",
"to",
"the",
"malignant",
"state",
"in",
"colorectal",
"cancer,",
"correction",
"of",
"only",
"a",
"single",
"defect",
" ",
"can",
"have",
"significant",
"effects",
"in",
"vivo",
"and/or",
"in",
"vitro."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
7,
8,
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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 chromosome 15 chromosomes 5q, 17p, and 18q . Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro. |
22899730 | [
"We",
"evaluated",
"the",
"association",
"between",
"the",
"BRAF",
"c.1799T>A",
"(p.V600E)",
"mutation",
"and",
"survival",
"in",
"individuals",
"with",
"incident",
"invasive",
"CRC",
"diagnosed",
"between",
"1997",
"and",
"2007",
"in",
"Western",
"Washington",
"State.",
"Tumor",
"specimens",
"were",
"tested",
"for",
"this",
"BRAF",
"mutation",
"and",
"MSI",
"status.",
"We",
"used",
"Cox",
"regression",
"to",
"estimate",
"HRs",
"and",
"95%",
"confidence",
"intervals",
"(CI)",
"for",
"the",
"association",
"between",
"BRAF",
" ",
"mutation",
" ",
"status",
"and",
"disease-specific",
"and",
"overall",
"survival.",
"Stratified",
"analyses",
"were",
"conducted",
"by",
"age,",
"sex,",
"tumor",
"site,",
"stage,",
"and",
"MSI",
" ",
"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,
0,
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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0
] | We evaluated the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status. |
18345036 | [] | [] | |
9731891 | [
"Microsatellite",
"instability",
"is",
"prone",
"to",
"occur",
"in",
"sporadic",
"right",
"colon",
"carcinoma",
"during",
"tumor",
"growth",
"and",
"is",
"not",
"associated",
"significantly",
"with",
"mutations",
"in",
"the",
"hMLH1",
"and",
"hMSH2",
"mismatch",
"repair",
"genes",
"or",
"in",
"the",
"p53",
"gene.",
"Concomitant",
"detection",
"of",
"microsatellite",
"instability",
"and",
"p53",
"mutations",
"in",
"right",
"colon",
"carcinoma",
"is",
"associated",
"with",
"the",
"presence",
"of",
"lymph",
"node",
"metastases."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 gene. Concomitant detection of microsatellite instability and p53 mutations in right colon carcinoma is associated with the presence of lymph node metastases. |
26302849 | [
"##",
"METHODS"
] | [
0,
0
] | ## METHODS |
22899730 | [
"We",
"evaluated",
"the",
"association",
"between",
"the",
"BRAF",
"c.1799T>A",
"(p.V600E)",
"mutation",
"and",
"survival",
"in",
"individuals",
"with",
"incident",
"invasive",
"CRC",
"diagnosed",
"between",
"1997",
"and",
"2007",
"in",
"Western",
"Washington",
"State.",
"Tumor",
"specimens",
"were",
"tested",
"for",
"this",
"BRAF",
"mutation",
"and",
"MSI",
"status.",
"We",
"used",
"Cox",
"regression",
"to",
"estimate",
"HRs",
"and",
"95%",
"confidence",
"intervals",
"(CI)",
"for",
"the",
"association",
"between",
"BRAF",
"mutation",
"status",
"and",
"disease-specific",
"and",
"overall",
"survival.",
"Stratified",
"analyses",
"were",
"conducted",
"by",
"age,",
"sex,",
"tumor",
"site,",
"stage,",
"and",
"MSI",
"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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status. |
18345036 | [
"We",
"previously",
"reported",
"that",
"actin",
"damage",
"by",
"treatment",
"with",
"an",
"actin-depolymerizing",
"agent",
"including",
"pectenotoxin-2",
"induces",
"Bim-mediated",
"apoptosis",
"in",
"p53-deficient",
"human",
"tumors.",
"In",
"this",
"study,",
"we",
"investigated",
"a",
"molecular",
"mechanism",
"underlying",
"Bim-mediated",
"apoptosis",
"of",
"p53-deficient",
"tumor",
"cells",
"following",
"actin",
"damage.",
"We",
"found",
"that",
"actin",
"inhibitors",
"increased",
"the",
"protein",
"levels",
"of",
"p53",
"and",
"p21",
"and",
"thereby",
"inactivated",
"both",
"Cdk2",
"and",
"Cdc2",
"kinases.",
"However,",
"p53-",
"or",
"p21-knockout",
"cells",
"fail",
"to",
"induce",
"p21",
"and",
"hence",
"kept",
"both",
"Cdk2",
"and",
"Cdc2",
"kinases",
"active",
"even",
"after",
"treatment",
"with",
"actin",
"inhibitor.",
"The",
"p53-",
"or",
"p21-knockout",
"cells",
"became",
"multinucleate",
"and",
"polyploidy",
"in",
"association",
"with",
"induction",
"of",
"apoptosis.",
"Expression",
"of",
"Bcl-x(L)",
"resulted",
"in",
"accumulation",
"of",
"polyploid",
"cells",
"in",
"association",
"with",
"inhibition",
"of",
"apoptosis.",
"However,",
"expression",
"of",
"a",
"dominant",
"negative",
"mutant",
"actin",
"actin",
" ",
"damage",
"by",
"treatment",
"with",
"an",
"actin-depolymerizing",
"agent",
"including",
"pectenotoxin-2",
"induces",
"Bim-mediated",
"apoptosis",
"in",
"p53",
"Bim",
"-mediated",
"apoptosis",
"in",
"p53-deficient",
"human",
"tumors.",
"In",
"this",
"study,",
"we",
"investigated",
"a",
"molecular",
"mechanism",
"underlying",
"Bim-mediated",
"apoptosis",
"of",
"p53-deficient",
"tumor",
"cells",
"following",
"actin",
"damage.",
"We",
"found",
"that",
"actin",
"inhibitors",
"increased",
"the",
"protein",
"levels",
"of",
"p53",
"and",
"p21",
"and",
"thereby",
"inactivated",
"both",
"Cdk2",
"and",
"Cdc2",
"kinases.",
"However,",
"p53-",
"or",
"p21-knockout",
"cells",
"fail",
"to",
"induce",
"p21",
"and",
"hence",
"kept",
"both",
"Cdk2",
"and",
"Cdc2",
"kinases",
"active",
"even",
"after",
"treatment",
"with",
"actin",
"inhibitor.",
"The",
"p53-",
"or",
"p21-knockout",
"cells",
"became",
"multinucleate",
"and",
"polyploidy",
"in",
"association",
"with",
"induction",
"of",
"apoptosis.",
"Expression",
"of",
"Bcl-x(L)",
"resulted",
"in",
"accumulation",
"of",
"polyploid",
"cells",
"in",
"association",
"with",
"inhibition",
"of",
"apoptosis.",
"However,",
"expression",
"of",
"a",
"dominant",
"negative",
"mutant",
"(Cdk2dn)",
"and",
"treatment",
"with",
"chemical",
"inhibitors",
"for",
"Cdk2",
"suppressed",
"not",
"only",
"accumulation",
"of",
"multinucleated",
"cells,",
"but",
"also",
"induction",
"of",
"Bim",
"expression",
"and",
"apoptosis.",
"Therefore,",
"these",
"results",
"suggest",
"that",
"Bim",
"Bim",
"-mediated",
"apoptosis",
"of",
"p53",
"-deficient",
"tumor",
"cells",
"following",
"actin",
"damage.",
"We",
"found",
"that",
"actin",
"inhibitors",
"increased",
"the",
"protein",
"levels",
"of",
"p53",
"and",
"p21",
"and",
"thereby",
"inactivated",
"both",
"Cdk2",
"and",
"Cdc2",
"kinases.",
"However,",
"p53-",
"or",
"p21-knockout",
"cells",
"fail",
"to",
"induce",
"p21",
"and",
"hence",
"kept",
"both",
"Cdk2",
"and",
"Cdc2",
"kinases",
"active",
"even",
"after",
"treatment",
"with",
"actin",
"inhibitor.",
"The",
"p53-",
"or",
"p21-knockout",
"cells",
"became",
"multinucleate",
"and",
"polyploidy",
"in",
"association",
"with",
"induction",
"of",
"apoptosis.",
"Expression",
"of",
"Bcl-x(L)",
"resulted",
"in",
"accumulation",
"of",
"polyploid",
"cells",
"in",
"association",
"with",
"inhibition",
"of",
"apoptosis.",
"However,",
"expression",
"of",
"a",
"dominant",
"negative",
"mutant",
"(Cdk2dn)",
"and",
"treatment",
"with",
"chemical",
"inhibitors",
"for",
"Cdk2",
"suppressed",
"not",
"only",
"accumulation",
"of",
"multinucleated",
"cells,",
"but",
"also",
"induction",
"of",
"Bim",
"expression",
"and",
"apoptosis.",
"Therefore,",
"these",
"results",
"suggest",
"that",
"Bim-mediated",
"apoptosis",
"following",
"actin",
"damage",
"due",
"to",
"deregulation",
"of",
"Cdk2",
"and",
"the",
"cell",
"cycle",
"by",
"the",
"absence",
"of",
"functional",
"p53."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
1,
1,
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,
1,
1,
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
] | We previously reported that actin damage by treatment with an actin-depolymerizing agent including pectenotoxin-2 induces Bim-mediated apoptosis in p53-deficient human tumors. In this study, we investigated a molecular mechanism underlying Bim-mediated apoptosis of p53-deficient tumor cells following actin damage. We found that actin inhibitors increased the protein levels of p53 and p21 and thereby inactivated both Cdk2 and Cdc2 kinases. However, p53- or p21-knockout cells fail to induce p21 and hence kept both Cdk2 and Cdc2 kinases active even after treatment with actin inhibitor. The p53- or p21-knockout cells became multinucleate and polyploidy in association with induction of apoptosis. Expression of Bcl-x(L) resulted in accumulation of polyploid cells in association with inhibition of apoptosis. However, expression of a dominant negative mutant actin actin damage by treatment with an actin-depolymerizing agent including pectenotoxin-2 induces Bim-mediated apoptosis in p53 Bim -mediated apoptosis in p53-deficient human tumors. In this study, we investigated a molecular mechanism underlying Bim-mediated apoptosis of p53-deficient tumor cells following actin damage. We found that actin inhibitors increased the protein levels of p53 and p21 and thereby inactivated both Cdk2 and Cdc2 kinases. However, p53- or p21-knockout cells fail to induce p21 and hence kept both Cdk2 and Cdc2 kinases active even after treatment with actin inhibitor. The p53- or p21-knockout cells became multinucleate and polyploidy in association with induction of apoptosis. Expression of Bcl-x(L) resulted in accumulation of polyploid cells in association with inhibition of apoptosis. However, expression of a dominant negative mutant (Cdk2dn) and treatment with chemical inhibitors for Cdk2 suppressed not only accumulation of multinucleated cells, but also induction of Bim expression and apoptosis. Therefore, these results suggest that Bim Bim -mediated apoptosis of p53 -deficient tumor cells following actin damage. We found that actin inhibitors increased the protein levels of p53 and p21 and thereby inactivated both Cdk2 and Cdc2 kinases. However, p53- or p21-knockout cells fail to induce p21 and hence kept both Cdk2 and Cdc2 kinases active even after treatment with actin inhibitor. The p53- or p21-knockout cells became multinucleate and polyploidy in association with induction of apoptosis. Expression of Bcl-x(L) resulted in accumulation of polyploid cells in association with inhibition of apoptosis. However, expression of a dominant negative mutant (Cdk2dn) and treatment with chemical inhibitors for Cdk2 suppressed not only accumulation of multinucleated cells, but also induction of Bim expression and apoptosis. Therefore, these results suggest that Bim-mediated apoptosis following actin damage due to deregulation of Cdk2 and the cell cycle by the absence of functional p53. |
8495305 | [] | [] | |
20459617 | [
"Estimates",
"suggest",
"that",
"up",
"to",
"30%",
"of",
"colorectal",
"cancers",
"(CRC)",
"may",
"develop",
"due",
"to",
"an",
"increased",
"genetic",
"risk.",
"The",
"mean",
"age",
"at",
"diagnosis",
"for",
"CRC",
"is",
"about",
"70",
"years.",
"Time",
"of",
"disease",
"onset",
"20",
"years",
"younger",
"than",
"the",
"mean",
"age",
"is",
"assumed",
"to",
"be",
"indicative",
"of",
"genetic",
"susceptibility.",
"We",
"have",
"compared",
"high",
"resolution",
"tumor",
"genome",
"copy",
"number",
"variation",
"(CNV)",
"(Roche",
"NimbleGen,",
"385",
"000",
"oligo",
"CGH",
"array)",
"in",
"microsatellite",
"stable",
"(MSS)",
"tumors",
"from",
"two",
"age",
"groups,",
"including",
"23",
"young",
"at",
"onset",
"patients",
"without",
"known",
"hereditary",
"syndromes",
"and",
"with",
"a",
"median",
"age",
"of",
"44",
"years",
"(range:",
"28-53)",
"and",
"17",
"elderly",
"patients",
"with",
"median",
"age",
"79",
"years",
"(range:",
"69-87).",
"Our",
"aim",
"was",
"to",
"identify",
"differences",
"in",
"the",
"tumor",
"genomes",
"between",
"these",
"groups",
"and",
"pinpoint",
"potential",
"susceptibility",
"loci.",
"Integration",
"analysis",
"of",
"CNV",
" ",
"and",
"genome",
"wide",
"mRNA",
"expression",
"data,",
"available",
"for",
"the",
"same",
"tumors,",
"was",
"performed",
"to",
"identify",
"a",
"restricted",
"candidate",
"gene",
"list."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Estimates suggest that up to 30% of colorectal cancers (CRC) may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV) (Roche NimbleGen, 385 000 oligo CGH array) in microsatellite stable (MSS) tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53) and 17 elderly patients with median age 79 years (range: 69-87). Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. |
14734469 | [
"BRAF",
"mutations",
"are",
"frequently",
"present",
"in",
"sporadic",
"colorectal",
"cancer",
"with",
"methylated",
"methylated",
" ",
"hMLH1,",
"whereas",
"only",
"4",
"of",
"91",
"(4%)",
"of",
"the",
"cell",
"lines",
"and",
"cancers",
"with",
"unmethylated",
"hMLH1",
"carried",
"the",
"mutations",
"(P",
"<",
"0.00001).",
"Sixteen",
"of",
"17",
"mutations",
" ",
"were",
"at",
"residue",
"599",
"methylated",
" ",
"hMLH1,",
"but",
"not",
"in",
"hereditary",
"nonpolyposis",
"colorectal",
"cancer.",
"\n\n\n",
"##",
"PURPOSE"
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
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,
3,
0,
0,
0,
7,
8,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | BRAF mutations are frequently present in sporadic colorectal cancer with methylated methylated hMLH1, whereas only 4 of 91 (4%) of the cell lines and cancers with unmethylated hMLH1 carried the mutations (P < 0.00001). Sixteen of 17 mutations were at residue 599 methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer.
## PURPOSE |
17389618 | [
"Dietary",
"folate",
"and",
"alcohol",
"consumption",
"as",
"well",
"as",
"polymorphic",
"variants",
"in",
"one-carbon",
"metabolism",
"genes",
"may",
"modulate",
"risk",
"of",
"colorectal",
"adenoma",
"through",
"aberrant",
"DNA",
"methylation",
"and",
"altered",
"nucleotide",
"synthesis",
"and",
"repair.",
"We",
"assessed",
"the",
"association",
"of",
"24",
"non-synonymous",
"single",
"nucleotide",
"polymorphisms",
"(nsSNPs)",
"in",
"13",
"genes",
"in",
"the",
"one-carbon",
"metabolism",
"pathway",
"and",
"risk",
"of",
"colorectal",
"adenoma",
"in",
"556",
"incident",
"cases",
"and",
"557",
"controls",
"nested",
"in",
"the",
"Nurses'",
"Health",
"Study.",
"Most",
"of",
"the",
"SNPs",
"were",
"not",
"associated",
"with",
"risk",
"of",
"colorectal",
"adenoma.",
"We",
"did,",
"however,",
"observe",
"a",
"modest",
"increased",
"risk",
"among",
"carriers",
"of",
"the",
"transcobalamin",
"(TCN)",
"II",
"259",
"Pro/Arg",
"+",
"Arg/Arg",
"variant",
"(odds",
"ratio",
"1.48,",
"95%",
"confidence",
"interval",
"1.09-2.02)",
"for",
"colorectal",
"adenoma.",
"The",
"TCN",
"II",
"Pro259Arg",
"polymorphism",
"may",
"affect",
"TCN",
"binding",
"and",
"transport",
"of",
"vitamin",
"B(12)",
"and",
"thus",
"warrants",
"further",
"investigation",
"of",
"its",
"biological",
"function.",
"In",
"addition,",
"the",
"methionine",
"synthase",
"reductase",
" ",
"(",
"MTRR",
")",
"Arg415Cys",
" ",
"and",
"MTRR",
" ",
"Ser284Thr",
"variant",
"carriers,",
"also",
"in",
"the",
"vitamin",
"B(12)",
"pathway,",
"have",
"suggestive",
"associations",
"with",
"advanced",
"colorectal",
"adenoma",
"(defined",
"as",
"being",
"larger",
"than",
"1",
"cm,",
"villous,",
"tubular-villous",
"or",
"carcinoma",
"in",
"situ",
"histology).",
"We",
"observed",
"significant",
"evidence",
"for",
"departure",
"from",
"multiplicative",
"interaction",
"for",
"the",
"betaine-homocysteine",
"methyltransferase",
"(",
"BHMT",
"Ser284Thr",
" ",
"variant",
"carriers,",
"also",
"in",
"the",
"vitamin",
"B(12)",
"pathway,",
"have",
"suggestive",
"associations",
"with",
"advanced",
"colorectal",
"adenoma",
"(defined",
"as",
"being",
"larger",
"than",
"1",
"cm,",
"villous,",
"tubular-villous",
"or",
"carcinoma",
"in",
"situ",
"histology).",
"We",
"observed",
"significant",
"evidence",
"for",
"departure",
"from",
"multiplicative",
"interaction",
"for",
"the",
"betaine-homocysteine",
"methyltransferase",
"(BHMT)",
"Arg239Gln",
" ",
"with",
"dietary",
"methyl",
"status",
"(based",
"on",
"intake",
"of",
"dietary",
"folate,",
"methionine",
"and",
"alcohol",
"intake)",
"in",
"relation",
"to",
"colorectal",
"adenoma;",
"no",
"such",
"interaction",
"was",
"observed",
"for",
"the",
"other",
"23",
"SNPs",
"non-synonymous",
"polymorphisms",
" ",
"in",
"the",
"one-carbon",
"metabolic",
"pathway",
"and",
"risk",
"of",
"colorectal",
"adenoma",
"in",
"the",
"Nurses'",
"Health",
"Study."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
1,
0,
13,
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,
1,
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,
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,
3,
3,
4,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Dietary folate and alcohol consumption as well as polymorphic variants in one-carbon metabolism genes may modulate risk of colorectal adenoma through aberrant DNA methylation and altered nucleotide synthesis and repair. We assessed the association of 24 non-synonymous single nucleotide polymorphisms (nsSNPs) in 13 genes in the one-carbon metabolism pathway and risk of colorectal adenoma in 556 incident cases and 557 controls nested in the Nurses' Health Study. Most of the SNPs were not associated with risk of colorectal adenoma. We did, however, observe a modest increased risk among carriers of the transcobalamin (TCN) II 259 Pro/Arg + Arg/Arg variant (odds ratio 1.48, 95% confidence interval 1.09-2.02) for colorectal adenoma. The TCN II Pro259Arg polymorphism may affect TCN binding and transport of vitamin B(12) and thus warrants further investigation of its biological function. In addition, the methionine synthase reductase ( MTRR ) Arg415Cys and MTRR Ser284Thr variant carriers, also in the vitamin B(12) pathway, have suggestive associations with advanced colorectal adenoma (defined as being larger than 1 cm, villous, tubular-villous or carcinoma in situ histology). We observed significant evidence for departure from multiplicative interaction for the betaine-homocysteine methyltransferase ( BHMT Ser284Thr variant carriers, also in the vitamin B(12) pathway, have suggestive associations with advanced colorectal adenoma (defined as being larger than 1 cm, villous, tubular-villous or carcinoma in situ histology). We observed significant evidence for departure from multiplicative interaction for the betaine-homocysteine methyltransferase (BHMT) Arg239Gln with dietary methyl status (based on intake of dietary folate, methionine and alcohol intake) in relation to colorectal adenoma; no such interaction was observed for the other 23 SNPs non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nurses' Health Study. |
9841584 | [
"##",
"DESIGN"
] | [
0,
0
] | ## DESIGN |
10439970 | [
"Marfan-like",
"habitus",
"and",
"familial",
"adenomatous",
"polyposis",
"in",
"two",
"unrelated",
"males:",
"a",
"significant",
"association?"
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Marfan-like habitus and familial adenomatous polyposis in two unrelated males: a significant association? |
23584879 | [
"We",
"evaluated",
"the",
"feasibility",
"of",
"an",
"automated",
"tablet",
"computer",
"application",
"providing",
"a",
"family",
"and",
"personal",
"history",
"based",
"cancer",
"risk",
"assessment",
"for",
"hereditary",
"breast,",
"ovarian,",
"endometrial",
"and",
"colorectal",
"cancers.",
"1,002",
"women",
"presenting",
"for",
"screening",
"mammography",
"and",
"1,000",
"presenting",
"for",
"ultrasound",
"were",
"offered",
"screening.",
"The",
"application",
"calculated",
"the",
"risk",
"of",
"BRCA",
"mutations",
" ",
"using",
"BRCA",
"BRCA",
" ",
"mutations",
"using",
"BRCAPRO,",
"Myriad",
"and",
"Tyrer-Cuzick",
"risk",
"assessment",
"models.",
"Lifetime",
"risk",
"of",
"breast",
"and",
"ovarian",
"cancer",
"was",
"assessed",
"with",
"the",
"BRCA",
"PRO,",
"Claus",
"and",
"Tyrer-Cuzick",
"models.",
"Colorectal",
"and",
"endometrial",
"cancer",
"risk",
"was",
"calculated",
"via",
"the",
"MMRpro",
"model.",
"Patients",
"were",
"identified",
"as",
"high-risk",
"based",
"on",
"thresholds",
"10%",
"or",
"greater",
"risk",
"for",
"carrying",
"genetic",
"mutations",
" ",
"or",
"20%",
"or",
"greater",
"lifetime",
"risk",
"of",
"breast",
"or",
"ovarian",
"cancer.",
"The",
"percent",
"of",
"women",
"found",
"to",
"be",
"high-risk",
"by",
"a",
"single",
"risk",
"assessment",
"tool",
"ranged",
"from",
"0.5",
"to",
"5.3%.",
"Combining",
"assessment",
"tools",
"found",
"9.3%",
"of",
"women",
"to",
"be",
"high-risk.",
"The",
"risk",
"assessments",
"performed",
"similarly",
"for",
"the",
"mammography",
"and",
"ultrasound",
"cohorts",
"with",
"yields",
"(combining",
"assessment",
"tools)",
"of",
"9.2",
"and",
"9.4%",
"respectively.",
"The",
"average",
"ages",
"of",
"all",
"the",
"high-risk",
"women",
"were",
"45.8",
"and",
"39.6",
"years",
"for",
"the",
"mammography",
"and",
"ultrasound",
"cohorts",
"respectively.",
"Difficulties",
"encountered",
"included",
"a",
"need",
"for",
"software",
"upgrade,",
"wireless",
"network",
"unreliability",
"and",
"hardware",
"theft.",
"Automated",
"family",
"history",
"screening",
"can",
"identify",
"women",
"probably",
"at",
"high-risk",
"for",
"hereditary",
"cancers",
"efficiently.",
"The",
"number",
"of",
"women",
"identified",
"is",
"increased",
"by",
"employing",
"multiple",
"risk",
"assessment",
"models",
"simultaneously.",
"Surveying",
"women",
"in",
"conjunction",
"with",
"ultrasound",
"identified",
"women",
"at",
"increased",
"risk",
"as",
"effectively",
"and",
"at",
"a",
"younger",
"age",
"than",
"with",
"screening",
"mammography."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
0,
1,
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,
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
] | We evaluated the feasibility of an automated tablet computer application providing a family and personal history based cancer risk assessment for hereditary breast, ovarian, endometrial and colorectal cancers. 1,002 women presenting for screening mammography and 1,000 presenting for ultrasound were offered screening. The application calculated the risk of BRCA mutations using BRCA BRCA mutations using BRCAPRO, Myriad and Tyrer-Cuzick risk assessment models. Lifetime risk of breast and ovarian cancer was assessed with the BRCA PRO, Claus and Tyrer-Cuzick models. Colorectal and endometrial cancer risk was calculated via the MMRpro model. Patients were identified as high-risk based on thresholds 10% or greater risk for carrying genetic mutations or 20% or greater lifetime risk of breast or ovarian cancer. The percent of women found to be high-risk by a single risk assessment tool ranged from 0.5 to 5.3%. Combining assessment tools found 9.3% of women to be high-risk. The risk assessments performed similarly for the mammography and ultrasound cohorts with yields (combining assessment tools) of 9.2 and 9.4% respectively. The average ages of all the high-risk women were 45.8 and 39.6 years for the mammography and ultrasound cohorts respectively. Difficulties encountered included a need for software upgrade, wireless network unreliability and hardware theft. Automated family history screening can identify women probably at high-risk for hereditary cancers efficiently. The number of women identified is increased by employing multiple risk assessment models simultaneously. Surveying women in conjunction with ultrasound identified women at increased risk as effectively and at a younger age than with screening mammography. |
24196785 | [
"PVT-1,",
"which",
"maps",
"to",
"8q24,",
"generates",
"antiapoptotic",
"activity",
"in",
"CRC,",
"and",
"abnormal",
"expression",
"of",
"PVT-1",
"was",
"a",
"prognostic",
"indicator",
"for",
"CRC",
"patients."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients. |
17454882 | [
"##",
"MATERIAL",
"AND",
"METHODS"
] | [
0,
0,
0,
0
] | ## MATERIAL AND METHODS |
22899730 | [
"Among",
"1,980",
"cases",
"tested,",
"12%",
"were",
"BRAF",
"c.1799T>A",
"(",
"p.V600E",
"BRAF",
" ",
"mutations",
"in",
"colorectal",
"cancer",
"(CRC)",
"are",
"disproportionately",
"observed",
"in",
"tumors",
"exhibiting",
"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,
13,
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
] | Among 1,980 cases tested, 12% were BRAF c.1799T>A ( p.V600E BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear. |
15702478 | [] | [] | |
8709782 | [
"Between",
"1956",
"and",
"mid-1995,",
"225",
"patients",
"registered",
"at",
"the",
"Netherlands",
"Polyposis",
"Registry",
"had",
"undergone",
"IRA.",
"In",
"87",
"of",
"them,",
"a",
"pathogenetic",
"mutation",
"was",
"detected.",
"72",
"patients",
"had",
"a",
"mutation",
"located",
"before",
"codon",
"1250",
" ",
"and",
"15",
"patients",
"after",
"this",
"codon.",
"The",
"cumulative",
"risk",
"of",
"rectal",
"cancer",
"20",
"years",
"after",
"surgery",
"was",
"12%,",
"and",
"at",
"that",
"time",
"42%",
"had",
"undergone",
"rectal",
"excision.",
"The",
"risk",
"of",
"secondary",
"surgery",
"was",
"higher",
"in",
"patients",
"with",
"mutations",
"in",
"the",
"region",
"after",
"codon",
"1250",
" ",
"than",
"in",
"patients",
"with",
"mutations",
"before",
"this",
"codon",
"(relative",
"risk",
"2.7,",
"p",
"<",
"0.05)."
] | [
0,
0,
0,
0,
0,
0,
0,
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,
7,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Between 1956 and mid-1995, 225 patients registered at the Netherlands Polyposis Registry had undergone IRA. In 87 of them, a pathogenetic mutation was detected. 72 patients had a mutation located before codon 1250 and 15 patients after this codon. The cumulative risk of rectal cancer 20 years after surgery was 12%, and at that time 42% had undergone rectal excision. The risk of secondary surgery was higher in patients with mutations in the region after codon 1250 than in patients with mutations before this codon (relative risk 2.7, p < 0.05). |
9731891 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
9731891 | [
"Microsatellite",
"instability",
"is",
"prone",
"to",
"occur",
"in",
"sporadic",
"right",
"colon",
"carcinoma",
"during",
"tumor",
"growth",
"and",
"is",
"not",
"associated",
"significantly",
"with",
"mutations",
"in",
"the",
"hMLH1",
"and",
"hMSH2",
"mismatch",
"repair",
"genes",
"or",
"in",
"the",
"p53",
"gene.",
"Concomitant",
"detection",
"of",
"microsatellite",
"instability",
"Microsatellite",
"instability",
" ",
"was",
"analyzed",
"with",
"five",
"microsatellite",
"markers",
"at",
"chromosome",
"18.",
"The",
"mismatch",
"repair",
"genes",
"hMLH1",
"and",
"hMSH2",
"hMLH1",
" ",
"and",
"hMSH2",
"were",
"studied",
"in",
"tumors",
"found",
"to",
"have",
"microsatellite",
"instability",
"by",
"PCR",
"and",
"sequencing."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
3,
4,
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
] | Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 gene. Concomitant detection of microsatellite instability Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing. |
9731891 | [
"Microsatellite",
"instability",
"is",
"prone",
"to",
"occur",
"in",
"sporadic",
"right",
"colon",
"carcinoma",
"during",
"tumor",
"growth",
"and",
"is",
"not",
"associated",
"significantly",
"with",
"mutations",
"in",
"the",
"hMLH1",
" ",
"and",
"hMSH2",
"mismatch",
"repair",
"genes",
"or",
"in",
"the",
"p53",
"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,
1,
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
] | Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 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. |
21128281 | [
"In",
"the",
"majority",
"of",
"colorectal",
"cancers",
"(CRCs)",
"under",
"clinical",
"suspicion",
"for",
"a",
"hereditary",
"cause,",
"the",
"disease-causing",
"genetic",
"factors",
"are",
"still",
"to",
"be",
"discovered.",
"To",
"identify",
"such",
"genetic",
"factors",
"we",
"stringently",
"selected",
"a",
"discovery",
"cohort",
"of",
"41",
"CRC",
"index",
"patients",
"with",
"microsatellite-stable",
"tumors.",
"All",
"patients",
"were",
"below",
"40",
"years",
"of",
"age",
"at",
"diagnosis",
"and/or",
"exhibited",
"an",
"overt",
"family",
"history.",
"We",
"employed",
"genome-wide",
"copy",
"number",
"profiling",
"using",
"high-resolution",
"SNP",
"arrays",
"on",
"germline",
"DNA,",
"which",
"resulted",
"in",
"the",
"identification",
"of",
"novel",
"copy",
"number",
"variants",
"(CNVs)",
"in",
"six",
"patients",
"(15%)",
"encompassing,",
"among",
"others,",
"the",
"cadherin",
"gene",
"CDH18,",
"the",
"bone",
"morphogenetic",
"protein",
"antagonist",
"family",
"gene",
"GREM1",
",",
"and",
"the",
"breakpoint",
"cluster",
"region",
"gene",
"BCR",
".",
"In",
"addition,",
"two",
"genomic",
"deletions",
" ",
"were",
"encountered",
"encompassing",
"two",
"microRNA",
"genes,",
"hsa-mir-491/KIAA1797",
"and",
"hsa-mir-646/AK309218.",
"None",
"of",
"these",
"CNVs",
"SNP",
"microsatellite-stable",
" ",
"tumors.",
"All",
"patients",
"were",
"below",
"40",
"years",
"of",
"age",
"at",
"diagnosis",
"and/or",
"exhibited",
"an",
"overt",
"family",
"history.",
"We",
"employed",
"genome-wide",
"copy",
"number",
"profiling",
"using",
"high-resolution",
"SNP",
"arrays",
"on",
"germline",
"DNA,",
"which",
"resulted",
"in",
"the",
"identification",
"of",
"novel",
"copy",
"number",
"variants",
"(CNVs)",
"in",
"six",
"patients",
"(15%)",
"encompassing,",
"among",
"others,",
"the",
"cadherin",
"gene",
"CDH18,",
"the",
"bone",
"morphogenetic",
"protein",
"antagonist",
"family",
"gene",
"GREM1,",
"and",
"the",
"breakpoint",
"cluster",
"region",
"gene",
"BCR.",
"In",
"addition,",
"two",
"genomic",
"deletions",
"were",
"encountered",
"encompassing",
"two",
"microRNA",
"genes,",
"hsa-mir-491/",
"KIAA1797",
" ",
"and",
"hsa-mir-646/",
"AK309218",
"copy",
"number",
"variants",
" ",
"in",
"familial",
"and",
"early-onset",
"colorectal",
"cancer",
"patients."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
1,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
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,
15,
0,
0,
0,
15,
3,
4,
4,
0,
0,
0,
0,
0,
0,
0,
0
] | In the majority of colorectal cancers (CRCs) under clinical suspicion for a hereditary cause, the disease-causing genetic factors are still to be discovered. To identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite-stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome-wide copy number profiling using high-resolution SNP arrays on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in six patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1 , and the breakpoint cluster region gene BCR . In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa-mir-491/KIAA1797 and hsa-mir-646/AK309218. None of these CNVs SNP microsatellite-stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome-wide copy number profiling using high-resolution SNP arrays on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in six patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1, and the breakpoint cluster region gene BCR. In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa-mir-491/ KIAA1797 and hsa-mir-646/ AK309218 copy number variants in familial and early-onset colorectal cancer patients. |
20198339 | [
"MUC2",
"Ras",
"PKC",
"/Ras/ERK/",
"CREB",
"ERK",
"/CREB,",
"PI3K/",
"Akt",
"PI3K",
"/Akt/IkappaB/NF-kappaB",
"and",
"p38/MSK1/CREB",
"pathways",
"and",
"negative",
"JNK/c-Jun/AP-1",
"pathway."
] | [
1,
1,
1,
0,
1,
1,
0,
0,
1,
1,
0,
0,
0,
0,
0,
0,
0,
0
] | MUC2 Ras PKC /Ras/ERK/ CREB ERK /CREB, PI3K/ Akt PI3K /Akt/IkappaB/NF-kappaB and p38/MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway. |
22899730 | [
"BRAF",
"mutation",
"status",
"and",
"survival",
"after",
"colorectal",
"cancer",
"diagnosis",
"according",
"to",
"patient",
"and",
"tumor",
"characteristics.",
"\n\n\n",
"##",
"BACKGROUND"
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | BRAF mutation status and survival after colorectal cancer diagnosis according to patient and tumor characteristics.
## BACKGROUND |
14734469 | [
"##",
"CONCLUSIONS"
] | [
0,
0
] | ## CONCLUSIONS |
22810479 | [] | [] | |
9476377 | [] | [] | |
19706845 | [
"The",
"results",
"of",
"this",
"study",
"suggest",
"that",
"rs671",
" ",
"A/A",
"and",
"the",
"first",
"reported",
"locus",
"rs1329149",
"rs1329149",
" ",
"of",
"CYP2E1",
" ",
"and",
"a",
"known",
"polymorphism",
"rs671",
" ",
"of",
"ALDH2",
" ",
"of",
"alcohol",
"metabolizing",
"enzymes",
"are",
"associated",
"with",
"colorectal",
"cancer",
"in",
"a",
"southwestern",
"Chinese",
"population.",
"\n\n\n",
"##",
"BACKGROUND"
] | [
0,
0,
0,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
11,
11,
0,
0,
1,
0,
0,
0,
0,
0,
11,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | The results of this study suggest that rs671 A/A and the first reported locus rs1329149 rs1329149 of CYP2E1 and a known polymorphism rs671 of ALDH2 of alcohol metabolizing enzymes are associated with colorectal cancer in a southwestern Chinese population.
## BACKGROUND |
19706845 | [
"Sixteen",
"tagSNPs",
"were",
"selected,",
"and",
"13",
"were",
"successfully",
"genotyped.",
"A",
"novel",
"CYP2E1",
"locus",
"rs1329149",
"and",
"a",
"known",
"ALDH2",
"locus",
"rs671",
"were",
"found",
"to",
"be",
"significantly",
"associated",
"with",
"CRC",
"risk.",
"The",
"adjusted",
"OR",
"was",
"1.86",
"(95%",
"CI,",
"1.12-3.09)",
"for",
"the",
"rs671",
"A/A",
"genotype",
"and",
"4.04",
"for",
"the",
"rs1329149",
" ",
"T/T",
"genotype",
"(95%",
"CI,",
"2.44-6.70),",
"compared",
"with",
"their",
"common",
"homozygous",
"genotypes.",
"Interaction",
"was",
"found",
"between",
"alcohol",
"consumption",
"and",
"gene",
"polymorphisms",
"on",
"CRC,",
"the",
"adjusted",
"OR",
"was",
"7.17",
"(95%",
"CI,",
"2.01-25.53)",
"for",
"drinking",
"habits",
"combined",
"with",
"rs671",
" ",
"A/A",
"or",
"rs1329149",
" ",
"T/T",
"genotype."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
11,
0,
0,
0,
11,
0,
0,
0
] | Sixteen tagSNPs were selected, and 13 were successfully genotyped. A novel CYP2E1 locus rs1329149 and a known ALDH2 locus rs671 were found to be significantly associated with CRC risk. The adjusted OR was 1.86 (95% CI, 1.12-3.09) for the rs671 A/A genotype and 4.04 for the rs1329149 T/T genotype (95% CI, 2.44-6.70), compared with their common homozygous genotypes. Interaction was found between alcohol consumption and gene polymorphisms on CRC, the adjusted OR was 7.17 (95% CI, 2.01-25.53) for drinking habits combined with rs671 A/A or rs1329149 T/T genotype. |
12534642 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
24568449 | [
"##",
"CONCLUSIONS"
] | [
0,
0
] | ## CONCLUSIONS |
23132392 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
9841584 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
16924054 | [
"##",
"OBSERVATIONS"
] | [
0,
0
] | ## OBSERVATIONS |
25029911 | [] | [] | |
8261516 | [
"A",
"subset",
"of",
"sporadic",
"colorectal",
"tumors",
"and",
"most",
"tumors",
"developing",
"in",
"hereditary",
"nonpolyposis",
"colorectal",
"cancer",
"patients",
"display",
"frequent",
"alterations",
"in",
"microsatellite",
"sequences.",
"Such",
"tumors",
"have",
"been",
"thought",
"to",
"manifest",
"replication",
"errors",
"(RER+),",
"but",
"the",
"basis",
"for",
"the",
"alterations",
"has",
"remained",
"conjectural.",
"We",
"demonstrate",
"that",
"the",
"mutation",
"rate",
"of",
"(CA)n",
"repeats",
"in",
"RER+",
"tumor",
"cells",
"is",
"at",
"least",
"100-fold",
"that",
"in",
"RER-",
"tumor",
"cells",
"and",
"show",
"by",
"in",
"vitro",
"assay",
"that",
"increased",
"mutability",
"of",
"RER+",
"cells",
"is",
"associated",
"with",
"a",
"profound",
"defect",
"in",
"strand-specific",
"mismatch",
"repair.",
"This",
"deficiency",
"was",
"observed",
"with",
"microsatellite",
"heteroduplexes",
"as",
"well",
"as",
"with",
"heteroduplexes",
"containing",
"single",
"base-base",
"mismatches",
"and",
"affected",
"an",
"early",
"step",
"in",
"the",
"repair",
"pathway.",
"Thus,",
"a",
"true",
"mutator",
"phenotype",
"exists",
"in",
"a",
"subset",
"of",
"tumor",
"cells,",
"the",
"responsible",
"defect",
"is",
"likely",
"to",
"cause",
"transitions",
"and",
"transversions",
"in",
"addition",
"to",
"microsatellite",
"single",
"base-base",
"mismatches",
" ",
"and",
"affected",
"an",
"early",
"step",
"in",
"the",
"repair",
"pathway.",
"Thus,",
"a",
"true",
"mutator",
"phenotype",
"exists",
"in",
"a",
"subset",
"of",
"tumor",
"cells,",
"the",
"responsible",
"defect",
"is",
"likely",
"to",
"cause",
"transitions",
"alterations",
" ",
"in",
"microsatellite",
"sequences.",
"Such",
"tumors",
"have",
"been",
"thought",
"to",
"manifest",
"replication",
"errors",
"(RER+),",
"but",
"the",
"basis",
"for",
"the",
"alterations",
"has",
"remained",
"conjectural.",
"We",
"demonstrate",
"that",
"the",
"mutation",
"rate",
"of",
"(CA)n",
"repeats",
"in",
"RER+",
"tumor",
"cells",
"is",
"at",
"least",
"100-fold",
"that",
"in",
"RER-",
"tumor",
"cells",
"and",
"show",
"by",
"in",
"vitro",
"assay",
"that",
"increased",
"mutability",
"of",
"RER+",
"cells",
"is",
"associated",
"with",
"a",
"profound",
"defect",
"in",
"strand-specific",
"mismatch",
"repair.",
"This",
"deficiency",
"was",
"observed",
"with",
"microsatellite",
"heteroduplexes",
"as",
"well",
"as",
"with",
"heteroduplexes",
"containing",
"single",
"base-base",
"mismatches",
"and",
"affected",
"an",
"early",
"step",
"in",
"the",
"repair",
"pathway.",
"Thus,",
"a",
"true",
"mutator",
"phenotype",
"exists",
"in",
"a",
"subset",
"of",
"tumor",
"cells,",
"the",
"responsible",
"defect",
"is",
"likely",
"to",
"cause",
"transitions",
"and",
"transversions",
" ",
"in",
"addition",
"to",
"microsatellite",
"alterations",
"Hypermutability",
" ",
"and",
"mismatch",
"repair",
"deficiency",
"in",
"RER+",
"tumor",
"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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
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,
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,
3,
0,
0,
0,
0,
0,
3,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | A subset of sporadic colorectal tumors and most tumors developing in hereditary nonpolyposis colorectal cancer patients display frequent alterations in microsatellite sequences. Such tumors have been thought to manifest replication errors (RER+), but the basis for the alterations has remained conjectural. We demonstrate that the mutation rate of (CA)n repeats in RER+ tumor cells is at least 100-fold that in RER- tumor cells and show by in vitro assay that increased mutability of RER+ cells is associated with a profound defect in strand-specific mismatch repair. This deficiency was observed with microsatellite heteroduplexes as well as with heteroduplexes containing single base-base mismatches and affected an early step in the repair pathway. Thus, a true mutator phenotype exists in a subset of tumor cells, the responsible defect is likely to cause transitions and transversions in addition to microsatellite single base-base mismatches and affected an early step in the repair pathway. Thus, a true mutator phenotype exists in a subset of tumor cells, the responsible defect is likely to cause transitions alterations in microsatellite sequences. Such tumors have been thought to manifest replication errors (RER+), but the basis for the alterations has remained conjectural. We demonstrate that the mutation rate of (CA)n repeats in RER+ tumor cells is at least 100-fold that in RER- tumor cells and show by in vitro assay that increased mutability of RER+ cells is associated with a profound defect in strand-specific mismatch repair. This deficiency was observed with microsatellite heteroduplexes as well as with heteroduplexes containing single base-base mismatches and affected an early step in the repair pathway. Thus, a true mutator phenotype exists in a subset of tumor cells, the responsible defect is likely to cause transitions and transversions in addition to microsatellite alterations Hypermutability and mismatch repair deficiency in RER+ tumor cells. |
23497483 | [
"##",
"CONCLUSIONS"
] | [
0,
0
] | ## CONCLUSIONS |
26302849 | [
"We",
"genotyped",
"seven",
"single",
"nucleotide",
"polymorphisms",
" ",
"(SNPs)",
"from",
"seven",
"genes.",
"We",
"selected",
"588",
"patients",
"with",
"gastric",
"cancer",
"and",
"449",
"with",
"colorectal",
"cancer,",
"along",
"with",
"703",
"healthy",
"controls.",
"All",
"these",
"SNPs",
"were",
"evaluated",
"using",
"the",
"χ²",
"test",
"and",
"genetic",
"model",
"analysis."
] | [
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
] | We genotyped seven single nucleotide polymorphisms (SNPs) from seven genes. We selected 588 patients with gastric cancer and 449 with colorectal cancer, along with 703 healthy controls. All these SNPs were evaluated using the χ² test and genetic model analysis. |
24120286 | [] | [] | |
9691992 | [
"Microsatellite",
"instability",
"of",
"DNA",
"samples",
"of",
"79",
"sporadic",
"colon",
"cancer",
"patients",
"were",
"analyzed.",
"These",
"samples",
"were",
"also",
"screened",
"to",
"search",
"mutations",
"in",
"the",
"repeat",
"sequences",
"in",
"the",
"gene",
"for",
"the",
"type",
"II",
"receptor",
"of",
"transforming",
"growth",
"factor-beta",
"(TGF-beta",
"RII)",
"using",
"polymerase",
"chain",
"reaction",
"(PCR),",
"electrophoresis",
"with",
"urea",
"gel,",
"and",
"PCR-single",
"strand",
"conformation",
"polymorphism",
"(PCR-SSCP)",
"method.",
"The",
"incidence",
"of",
"microsatellite",
"instability,",
"defined",
"as",
"severe",
"replication",
"error",
"phenotype",
"(RER)",
"with",
"microsatellite",
"alterations",
"in",
"more",
"than",
"three",
"loci,",
"was",
"6%.",
"Deletion",
"and",
"insertion",
"of",
"an",
"A",
"residue",
"in",
"the",
"(A)10",
"region,",
"which",
"cause",
"frameshift",
"mutation,",
"were",
"found",
"in",
"four",
"samples",
"and",
"their",
"incidence",
"in",
"the",
"samples",
"with",
"microsatellite",
"instability",
"was",
"80%.",
"A",
"novel",
"nucleotide",
"substitution",
"of",
"T",
"for",
"G",
"Microsatellite",
"instability",
"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,
3,
4,
4,
4,
4,
4,
3,
4,
3,
4,
0
] | Microsatellite instability of DNA samples of 79 sporadic colon cancer patients were analyzed. These samples were also screened to search mutations in the repeat sequences in the gene for the type II receptor of transforming growth factor-beta (TGF-beta RII) using polymerase chain reaction (PCR), electrophoresis with urea gel, and PCR-single strand conformation polymorphism (PCR-SSCP) method. The incidence of microsatellite instability, defined as severe replication error phenotype (RER) with microsatellite alterations in more than three loci, was 6%. Deletion and insertion of an A residue in the (A)10 region, which cause frameshift mutation, were found in four samples and their incidence in the samples with microsatellite instability was 80%. A novel nucleotide substitution of T for G Microsatellite instability microsatellite instability . |
20646601 | [
"##",
"METHODS"
] | [
0,
0
] | ## METHODS |
22810479 | [
":",
"We",
"searched",
"PubMed,",
"Embase,",
"and",
"the",
"Cochrane",
"databases",
"from",
"January",
"1992",
"to",
"November",
"2011."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | : We searched PubMed, Embase, and the Cochrane databases from January 1992 to November 2011. |
26925673 | [
"##",
"CONCLUSIONS"
] | [
0,
0
] | ## CONCLUSIONS |
14645426 | [
"In",
"five",
"of",
"22",
"patients",
"with",
"a",
"positive",
"first-degree",
"family",
"history",
"for",
"hereditary",
"nonpolyposis",
"colorectal",
"cancer",
"(HNPCC)-related",
"cancers,",
"pathogenic",
"germline",
"mutations",
"mutation",
" ",
"analysis.",
"\n\n\n",
"##",
"PURPOSE"
] | [
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
] | In five of 22 patients with a positive first-degree family history for hereditary nonpolyposis colorectal cancer (HNPCC)-related cancers, pathogenic germline mutations mutation analysis.
## PURPOSE |
9841584 | [
"##",
"MEASUREMENTS"
] | [
0,
0
] | ## MEASUREMENTS |
22899730 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
8187091 | [
"Mutation",
"of",
"the",
"adenomatous",
"polyposis",
"coli",
"(APC)",
"gene",
"was",
"analyzed",
"in",
"500",
"colorectal",
"tumors",
"from",
"70",
"familial",
"adenomatous",
"polyposis",
"(FAP)",
"and",
"102",
"non-FAP",
"patients",
"and",
"in",
"normal",
"tissues",
"from",
"119",
"FAP",
"patients,",
"using",
"polymerase",
"chain",
"reaction-single-strand",
"conformation",
"polymorphism",
"and",
"direct",
"sequencing",
"methods.",
"These",
"tumors",
"were",
"histopathologically",
"diagnosed.",
"Sixty-eight",
"germ",
"line",
"mutations",
"(62%",
"deletion,",
"9%",
"insertion,",
"and",
"29%",
"single-base",
"substitution)",
"and",
"241",
"somatic",
"mutations",
"(56%",
"deletion,",
"12%",
"insertion,",
"and",
"32%",
"single-base",
"substitution)",
"were",
"detected.",
"All",
"mutations",
"formed",
"stop",
"codons",
"resulting",
"in",
"truncated",
"APC",
"proteins,",
"except",
"for",
"one",
"germ",
"line",
"mutation.",
"Differences",
"were",
"found",
"between",
"somatic",
"and",
"germ",
"line",
"mutations,",
"including",
"3",
"new",
"hot",
"spots",
"of",
"mutation",
"at",
"codons",
"1378,",
"1450,",
"and",
"1487-1490,",
"which",
"frequently",
"occurred",
"in",
"somatic",
"mutations",
"but",
"not",
"in",
"germ",
"lines.",
"The",
"frequency",
"of",
"mutation",
"in",
"each",
"histopathological",
"type",
"of",
"FAP",
"tumor",
"was",
"53%",
"in",
"moderate",
"adenoma,",
"64%",
"in",
"severe",
"adenoma,",
"52%",
"in",
"intramucosal",
"carcinoma,",
"and",
"33%",
"in",
"invasive",
"carcinoma,",
"whereas",
"the",
"loss",
"of",
"heterozygosity",
"including",
"the",
"APC",
"gene",
"increased",
"with",
"development",
"to",
"each",
"histopathological",
"type.",
"A",
"similar",
"tendency",
"was",
"observed",
"in",
"non-FAP",
"tumors.",
"Additionally,",
"we",
"found",
"10",
"FAP",
"tumors",
"that",
"had",
"both",
"somatic",
"mutation",
"and",
"loss",
"of",
"heterozygosity.",
"These",
"tumors",
"were",
"assumed",
"to",
"have",
"developed",
"from",
"moderate",
"adenomas",
"with",
"germ",
"line",
"and",
"somatic",
"mutations,",
"followed",
"by",
"deletion",
"of",
"the",
"allele",
"with",
"germ",
"line",
"mutation.",
"These",
"results",
"suggest",
"that",
"inactivation",
"of",
"the",
"APC",
"gene",
"by",
"two",
"mutations",
"mutations",
"mutation",
" ",
"of",
"the",
"adenomatous",
"polyposis",
"coli",
"gene",
"in",
"colorectal",
"tumors."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Mutation of the adenomatous polyposis coli (APC) gene was analyzed in 500 colorectal tumors from 70 familial adenomatous polyposis (FAP) and 102 non-FAP patients and in normal tissues from 119 FAP patients, using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing methods. These tumors were histopathologically diagnosed. Sixty-eight germ line mutations (62% deletion, 9% insertion, and 29% single-base substitution) and 241 somatic mutations (56% deletion, 12% insertion, and 32% single-base substitution) were detected. All mutations formed stop codons resulting in truncated APC proteins, except for one germ line mutation. Differences were found between somatic and germ line mutations, including 3 new hot spots of mutation at codons 1378, 1450, and 1487-1490, which frequently occurred in somatic mutations but not in germ lines. The frequency of mutation in each histopathological type of FAP tumor was 53% in moderate adenoma, 64% in severe adenoma, 52% in intramucosal carcinoma, and 33% in invasive carcinoma, whereas the loss of heterozygosity including the APC gene increased with development to each histopathological type. A similar tendency was observed in non-FAP tumors. Additionally, we found 10 FAP tumors that had both somatic mutation and loss of heterozygosity. These tumors were assumed to have developed from moderate adenomas with germ line and somatic mutations, followed by deletion of the allele with germ line mutation. These results suggest that inactivation of the APC gene by two mutations mutations mutation of the adenomatous polyposis coli gene in colorectal tumors. |
20661832 | [
"Hydrophobic",
"bile",
"acid-induced",
"micronuclei",
"formation,",
"mitotic",
"perturbations,",
"and",
"decreases",
"in",
"spindle",
"checkpoint",
"proteins:",
"relevance",
"to",
"genomic",
"instability",
"in",
"colon",
"carcinogenesis."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Hydrophobic bile acid-induced micronuclei formation, mitotic perturbations, and decreases in spindle checkpoint proteins: relevance to genomic instability in colon carcinogenesis. |
9841584 | [
"Decision",
"about",
"a",
"cancer",
"prevention",
"strategy",
"at",
"the",
"time",
"of",
"a",
"positive",
"result",
"on",
"genetic",
"testing."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Decision about a cancer prevention strategy at the time of a positive result on genetic testing. |
9439149 | [
"RER-positive",
"phenotypes",
"were",
"found",
"in",
"17",
"(22.1%)",
"of",
"77",
"cases.",
"In",
"young",
"patients",
"(under",
"40",
"years)",
"RER-positive",
"phenotype",
"was",
"found",
"in",
"9",
"(22.5%)",
"of",
"40",
"cases,",
"and",
"in",
"elderly",
"patients",
"8",
"(21.6%)",
"of",
"37",
"cases.",
"Moderately",
"differentiated",
"carcinoma",
"revealed",
"a",
"significantly",
"high",
"frequency",
"of",
"RER-positive",
"phenotype",
"than",
"well",
"differentiated",
"carcinoma(p",
"<",
"0.001).",
"Tumors",
"arising",
"from",
"the",
"middle",
"third",
"(p",
"<",
"0.001)",
"or",
"lower",
"third",
"(p",
"<",
"0.001)",
"revealed",
"higher",
"frequency",
"of",
"RER-positive",
"phenotype",
"than",
"the",
"tumors",
"arising",
"from",
"the",
"upper",
"third",
"of",
"the",
"stomach.",
"The",
"RER-positive",
"phenotype",
"was",
"not",
"significantly",
"affected",
"by",
"the",
"sex,",
"histologic",
"type",
"or",
"stage",
"of",
"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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 phenotypes were found in 17 (22.1%) of 77 cases. In young patients (under 40 years) RER-positive phenotype was found in 9 (22.5%) of 40 cases, and in elderly patients 8 (21.6%) of 37 cases. Moderately differentiated carcinoma revealed a significantly high frequency of RER-positive phenotype than well differentiated carcinoma(p < 0.001). Tumors arising from the middle third (p < 0.001) or lower third (p < 0.001) revealed higher frequency of RER-positive phenotype than the tumors arising from the upper third of the stomach. The RER-positive phenotype was not significantly affected by the sex, histologic type or stage of carcinoma. |
26925673 | [
"##",
"MATERIALS",
"AND",
"METHODS"
] | [
0,
0,
0,
0
] | ## MATERIALS AND METHODS |
9476377 | [
"##",
"METHODS",
"AND",
"RESULTS"
] | [
0,
0,
0,
0
] | ## METHODS AND RESULTS |
18554281 | [
"Colorectal",
"cancer",
"in",
"HNPCC:",
"cumulative",
"lifetime",
"incidence,",
"survival",
"and",
"tumour",
"distribution.",
"A",
"report",
"of",
"121",
"families",
"with",
"proven",
"mutations."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations. |
25374237 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
26302849 | [
"We",
"genotyped",
"seven",
"single",
"nucleotide",
"polymorphisms",
"(SNPs)",
"from",
"seven",
"genes.",
"We",
"selected",
"588",
"patients",
"with",
"gastric",
"cancer",
"and",
"449",
"with",
"colorectal",
"cancer,",
"along",
"with",
"703",
"healthy",
"controls.",
"All",
"these",
"SNPs",
"were",
"evaluated",
"using",
"the",
"χ²",
"test",
"and",
"genetic",
"model",
"analysis."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 genotyped seven single nucleotide polymorphisms (SNPs) from seven genes. We selected 588 patients with gastric cancer and 449 with colorectal cancer, along with 703 healthy controls. All these SNPs were evaluated using the χ² test and genetic model analysis. |
22810479 | [
":",
"To",
"derive",
"a",
"more",
"precise",
"estimation",
"of",
"the",
"prognostic",
"significance",
"of",
"K-ras",
" ",
"gene",
"mutations",
",",
"a",
"systematic",
"review",
"and",
"meta-analysis",
"were",
"performed."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0
] | : To derive a more precise estimation of the prognostic significance of K-ras gene mutations , a systematic review and meta-analysis were performed. |
19706845 | [
"A",
"hospital-based",
"case-control",
"study",
"of",
"440",
"CRC",
"patients",
"and",
"800",
"cancer-free",
"controls",
"was",
"conducted.",
"Personal",
"information",
"was",
"collected",
"by",
"a",
"Semi-Quantitative",
"Food",
"Frequency",
"Questionnaire.",
"The",
"tagSNPs",
"were",
"screened",
"in",
"the",
"HapMap",
"with",
"Haploview",
"by",
"setting",
"the",
"minor",
"allele",
"frequency",
"at",
"0.03",
"with",
"the",
"highest",
"score",
"of",
"r(2)",
"form",
"each",
"block.",
"Genotypes",
"were",
"identified",
"by",
"using",
"the",
"SNPLex",
"System.",
"Both",
"crude",
"and",
"adjusted",
"odds",
"ratio",
"(OR)",
"and",
"95%",
"confidence",
"interval",
"(CI)",
"were",
"used",
"to",
"evaluate",
"the",
"risk",
"of",
"each",
"SNP."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 hospital-based case-control study of 440 CRC patients and 800 cancer-free controls was conducted. Personal information was collected by a Semi-Quantitative Food Frequency Questionnaire. The tagSNPs were screened in the HapMap with Haploview by setting the minor allele frequency at 0.03 with the highest score of r(2) form each block. Genotypes were identified by using the SNPLex System. Both crude and adjusted odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risk of each SNP. |
22810479 | [
":",
"The",
"effect",
"of",
"K-ras",
" ",
"gene",
"mutations",
" ",
"on",
"the",
"overall",
"survival",
"was",
"measured",
"by",
"the",
"HR",
"and",
"95%",
"CIs."
] | [
0,
0,
0,
0,
1,
0,
0,
3,
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. |
27070770 | [
"Familial",
"adenomatous",
"polyposis",
"(FAP)",
"and",
"Peutz-Jeghers",
"syndrome",
"are",
"genetic",
"diseases",
"characterized",
"by",
"gastrointestinal",
"polyps,",
"extraintestinal",
"manifestations,",
"and",
"autosomal",
"dominant",
"inheritance.",
"The",
"carriers",
"of",
"these",
"diseases",
"from",
"early",
"childhood",
"are",
"at",
"risk",
"for",
"neoplasias",
"at",
"different",
"sites,",
"which",
"are",
"symptomatic",
"at",
"various",
"ages."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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) and Peutz-Jeghers syndrome are genetic diseases characterized by gastrointestinal polyps, extraintestinal manifestations, and autosomal dominant inheritance. The carriers of these diseases from early childhood are at risk for neoplasias at different sites, which are symptomatic at various ages. |
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. |
26416897 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
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). |
26302849 | [
"Gastric",
"and",
"colorectal",
"cancers",
"have",
"a",
"major",
"impact",
"on",
"public",
"health,",
"and",
"are",
"the",
"most",
"common",
"malignant",
"tumors",
"in",
"China.",
"The",
"aim",
"of",
"this",
"research",
"was",
"to",
"study",
"whether",
"polymorphisms",
" ",
"of",
"CHCHD3P1-HSP90AB7P",
",",
"GRID1,",
"HSPA12A,",
"PRLHR,",
"SBF2,",
"POLD3",
"and",
"C11orf93-C11orf92",
"genes",
"are",
"associated",
"with",
"the",
"risk",
"of",
"gastric",
"and",
"colorectal",
"cancers",
"in",
"the",
"Chinese",
"Han",
"population."
] | [
0,
0,
0,
0,
0,
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,
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
] | Gastric and colorectal cancers have a major impact on public health, and are the most common malignant tumors in China. The aim of this research was to study whether polymorphisms of CHCHD3P1-HSP90AB7P , GRID1, HSPA12A, PRLHR, SBF2, POLD3 and C11orf93-C11orf92 genes are associated with the risk of gastric and colorectal cancers in the Chinese Han population. |
7905818 | [
"Predictive",
"carrier",
"testing",
"for",
"the",
"inherited",
"disorder",
"of",
"familial",
"adenomatous",
"polyposis",
"(FAP)",
"can",
"be",
"conducted",
"using",
"DNA",
"markers",
"linked",
"to",
"the",
"FAP",
"locus",
".",
"The",
"presence",
"of",
"characteristic",
"hypertrophic",
"retinal",
"lesions",
"has",
"been",
"advocated",
"as",
"useful",
"biomarkers",
"for",
"FAP.",
"We",
"have",
"compared",
"molecular",
"linkage",
"and",
"retinal",
"screening",
"techniques",
"by",
"evaluating",
"the",
"presymptomatic",
"carrier",
"risk",
"of",
"40",
"at-risk",
"individuals",
"from",
"15",
"FAP",
"families.",
"Linkage",
"analysis",
"was",
"informative",
"in",
"all",
"and",
"retinal",
"lesion",
"analysis",
"in",
"25",
"cases.",
"For",
"informative",
"at-risk",
"population,",
"predictive",
"diagnosis",
"by",
"both",
"techniques",
"was",
"completely",
"concordant",
"and",
"identified",
"15",
"members",
"at",
"\"high\"",
"and",
"10",
"at",
"\"low\"",
"risk",
"of",
"inheriting",
"FAP.",
"Because",
"of",
"the",
"unique",
"advantages",
"offered",
"by",
"each",
"technique,",
"a",
"strategy",
"integrating",
"both",
"techniques",
"will",
"increase",
"the",
"number",
"of",
"FAP",
"families",
"that",
"can",
"be",
"screened",
"presymptomatically.",
"Identification",
"of",
"individuals",
"at",
"high",
"risk",
"of",
"polyposis",
"will",
"improve",
"their",
"clinical",
"surveillance",
"and",
"further",
"reduce",
"the",
"incidence",
"of",
"colorectal",
"cancer",
"in",
"FAP",
"families."
] | [
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
] | Predictive carrier testing for the inherited disorder of familial adenomatous polyposis (FAP) can be conducted using DNA markers linked to the FAP locus . The presence of characteristic hypertrophic retinal lesions has been advocated as useful biomarkers for FAP. We have compared molecular linkage and retinal screening techniques by evaluating the presymptomatic carrier risk of 40 at-risk individuals from 15 FAP families. Linkage analysis was informative in all and retinal lesion analysis in 25 cases. For informative at-risk population, predictive diagnosis by both techniques was completely concordant and identified 15 members at "high" and 10 at "low" risk of inheriting FAP. Because of the unique advantages offered by each technique, a strategy integrating both techniques will increase the number of FAP families that can be screened presymptomatically. Identification of individuals at high risk of polyposis will improve their clinical surveillance and further reduce the incidence of colorectal cancer in FAP families. |
14645426 | [
"Endometrial",
"cancer",
"patients",
"(N",
"=",
"58),",
"who",
"were",
"diagnosed",
"at",
"less",
"than",
"50",
"years",
"of",
"age,",
"were",
"included",
"and",
"questioned",
"about",
"their",
"family",
"history.",
"Mutation",
"analysis",
"of",
"the",
"MLH1",
",",
"MSH2",
",",
"and",
"MSH6",
" ",
"genes",
"was",
"performed",
"(denaturing",
"gradient",
"gel",
"electrophoresis",
"and",
"sequence",
"analysis",
"to",
"detect",
"small",
"mutations",
"and",
"multiplex",
"ligation-dependent",
"probe",
"amplification",
"to",
"detect",
"large",
"deletions",
"or",
"duplications).",
"For",
"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,
1,
0,
1,
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
] | Endometrial cancer patients (N = 58), who were diagnosed at less than 50 years of age, were included and questioned about their family history. Mutation analysis of the MLH1 , MSH2 , and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and multiplex ligation-dependent probe amplification to detect large deletions or duplications). For MSI analysis, five consensus markers were used, and immunostaining of the three MMR proteins was performed. |
9476377 | [
"##",
"CONCLUSIONS"
] | [
0,
0
] | ## CONCLUSIONS |
25421761 | [] | [] | |
26302849 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |
20646601 | [
"Of",
"208",
"cases,",
"91",
"cases",
"of",
"K-ras",
"gene",
"mutation",
"were",
"detected.",
"The",
"12",
"or",
"13",
"codon",
"had",
"a",
"mutation",
"rate",
"of",
"43.8%.",
"There",
"were",
"no",
"significant",
"differences",
"in",
"gender,",
"tumor",
"location,",
"histopathological",
"grading",
"and",
"Duke's",
"stage",
"between",
"the",
"wild",
"and",
"mutated",
"groups."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Of 208 cases, 91 cases of K-ras gene mutation were detected. The 12 or 13 codon had a mutation rate of 43.8%. There were no significant differences in gender, tumor location, histopathological grading and Duke's stage between the wild and mutated groups. |
8709782 | [
"We",
"evaluated",
"the",
"incidence",
"of",
"rectal",
"cancer",
"in",
"polyposis",
"patients",
"who",
"had",
"undergone",
"IRA,",
"and",
"examined",
"whether",
"the",
"requirement",
"for",
"subsequent",
"rectal",
"excision",
"because",
"of",
"cancer",
"or",
"uncontrollable",
"polyps",
"was",
"related",
"to",
"the",
"site",
"of",
"mutation."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 the incidence of rectal cancer in polyposis patients who had undergone IRA, and examined whether the requirement for subsequent rectal excision because of cancer or uncontrollable polyps was related to the site of mutation. |
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",
"mutations",
" ",
"have",
"been",
"reported",
"in",
"about",
"40%",
"of",
"colorectal",
"cancer",
"patients.",
"These",
"mutations",
"have",
"always",
"been",
"responsible",
"for",
"enhancing",
"malignancy",
"and",
"silencing",
"them",
"is",
"associated",
"with",
"attenuation",
"of",
"tumorigenicity.",
"Among",
"downstream",
"effectors",
"are",
"the",
"RAF/MEK/ERK",
"and",
"the",
"PI3K/Akt",
"signaling",
"pathways.",
"PI3K/Akt",
"signaling",
"leads",
"to",
"reduction",
"of",
"apoptosis,",
"stimulated",
"cell",
"growth",
"and",
"enhanced",
"proliferation.",
"Ellagic",
"acid",
"(EA),",
"a",
"naturally",
"occurring",
"antioxidant,",
"has",
"recently",
"emerged",
"as",
"a",
"promising",
"anti-cancer",
"agent."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
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 mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent. |
22810479 | [
":",
"The",
"heterogeneity",
"in",
"the",
"study",
"populations",
"is",
"a",
"potential",
"problem,",
"the",
"use",
"of",
"different",
"staging",
"systems",
"or",
"small",
"groups",
"of",
"different",
"stages",
"may",
"contribute",
"to",
"heterogeneity,",
"and",
"residual",
"confounding",
"may",
"have",
"influenced",
"the",
"results",
"in",
"those",
"studies",
"that",
"did",
"not",
"completely",
"adjust",
"for",
"other",
"factors."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 heterogeneity in the study populations is a potential problem, the use of different staging systems or small groups of different stages may contribute to heterogeneity, and residual confounding may have influenced the results in those studies that did not completely adjust for other factors. |
19706845 | [
"##",
"METHODS"
] | [
0,
0
] | ## METHODS |
1347643 | [] | [] | |
6300869 | [
"Homogeneously",
"staining",
"chromosomal",
"regions",
"contain",
"amplified",
"copies",
"of",
"an",
"abundantly",
"expressed",
"cellular",
"oncogene",
"(c-myc)",
"in",
"malignant",
"neuroendocrine",
"cells",
"from",
"a",
"human",
"colon",
"carcinoma."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. |
1299227 | [
"Nuclear",
"DNA",
"content",
"was",
"measured",
"in",
"72",
"colorectal",
"carcinomas",
"using",
"single-cell",
"microspectrophotometry",
"on",
"Feulgen-stained",
"smears.",
"Four",
"samples",
"were",
"analyzed",
"from",
"each",
"tumor.",
"Patients",
"were",
"followed",
"for",
"41-65",
"months",
"(average,",
"53).",
"DNA",
"heterogeneity",
"(both",
"aneuploid",
"and",
"nonaneuploid",
"patterns)",
"was",
"present",
"in",
"44%",
"of",
"the",
"cases.",
"Sixty-eight",
"percent",
"of",
"the",
"tumors",
"showed",
"an",
"aneuploid",
"DNA",
"pattern",
"in",
"at",
"least",
"one",
"of",
"the",
"samples.",
"Patients",
"with",
"nonaneuploid",
" ",
"tumors",
"tended",
"to",
"have",
"a",
"survival",
"advantage",
"over",
"patients",
"with",
"homogeneously",
"aneuploid",
"tumors",
"and",
"demonstrated",
"a",
"significantly",
"longer",
"disease-free",
"survival.",
"The",
"DNA",
"ploidy",
"pattern",
"is",
"of",
"potential",
"value",
"in",
"conjunction",
"with",
"histopathologic",
"prognostic",
"parameters",
"in",
"colorectal",
"carcinoma.",
"Since",
"colorectal",
"tumors",
"exhibit",
"pronounced",
"DNA",
"heterogeneity",
",",
"multiple",
"samples",
"are",
"required",
"from",
"each",
"tumor",
"to",
"permit",
"a",
"proper",
"evaluation",
"of",
"its",
"DNA",
"pattern.",
"The",
"DNA",
"heterogeneity",
"DNA",
"heterogeneity",
" ",
"(both",
"aneuploid",
"and",
"nonaneuploid",
"aneuploid",
" ",
"and",
"nonaneuploid",
"patterns)",
"was",
"present",
"in",
"44%",
"of",
"the",
"cases.",
"Sixty-eight",
"percent",
"of",
"the",
"tumors",
"showed",
"an",
"aneuploid",
" ",
"DNA",
"pattern",
"in",
"at",
"least",
"one",
"of",
"the",
"samples.",
"Patients",
"with",
"nonaneuploid",
"tumors",
"tended",
"to",
"have",
"a",
"survival",
"advantage",
"over",
"patients",
"with",
"homogeneously",
"aneuploid",
"DNA",
"ploidy",
"pattern",
" ",
"and",
"prognosis",
"with",
"reference",
"to",
"tumor",
"DNA",
"heterogeneity",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
4,
3,
4,
0,
0,
0,
0,
3,
3,
0,
0,
0,
0,
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,
3,
3,
4,
4,
0,
0,
0,
0,
0,
0,
0,
3,
4,
0
] | Nuclear DNA content was measured in 72 colorectal carcinomas using single-cell microspectrophotometry on Feulgen-stained smears. Four samples were analyzed from each tumor. Patients were followed for 41-65 months (average, 53). DNA heterogeneity (both aneuploid and nonaneuploid patterns) was present in 44% of the cases. Sixty-eight percent of the tumors showed an aneuploid DNA pattern in at least one of the samples. Patients with nonaneuploid tumors tended to have a survival advantage over patients with homogeneously aneuploid tumors and demonstrated a significantly longer disease-free survival. The DNA ploidy pattern is of potential value in conjunction with histopathologic prognostic parameters in colorectal carcinoma. Since colorectal tumors exhibit pronounced DNA heterogeneity , multiple samples are required from each tumor to permit a proper evaluation of its DNA pattern. The DNA heterogeneity DNA heterogeneity (both aneuploid and nonaneuploid aneuploid and nonaneuploid patterns) was present in 44% of the cases. Sixty-eight percent of the tumors showed an aneuploid DNA pattern in at least one of the samples. Patients with nonaneuploid tumors tended to have a survival advantage over patients with homogeneously aneuploid DNA ploidy pattern and prognosis with reference to tumor DNA heterogeneity . |
21128281 | [
"Identification",
"of",
"candidate",
"predisposing",
"copy",
"number",
"variants",
"in",
"familial",
"and",
"early-onset",
"colorectal",
"cancer",
"patients."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | Identification of candidate predisposing copy number variants in familial and early-onset colorectal cancer patients. |
22899730 | [
"We",
"evaluated",
"the",
"association",
"between",
"the",
"BRAF",
"c.1799T>A",
"(p.V600E)",
"mutation",
"and",
"survival",
"in",
"individuals",
"with",
"incident",
"invasive",
"CRC",
"diagnosed",
"between",
"1997",
"and",
"2007",
"in",
"Western",
"Washington",
"State.",
"Tumor",
"specimens",
"were",
"tested",
"for",
"this",
"BRAF",
"mutation",
"and",
"MSI",
"status.",
"We",
"used",
"Cox",
"regression",
"to",
"estimate",
"HRs",
"and",
"95%",
"confidence",
"intervals",
"(CI)",
"for",
"the",
"association",
"between",
"BRAF",
"mutation",
"status",
"and",
"disease-specific",
"and",
"overall",
"survival.",
"Stratified",
"analyses",
"were",
"conducted",
"by",
"age,",
"sex,",
"tumor",
"site,",
"stage,",
"and",
"MSI",
"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,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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 the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status. |
22810479 | [
"##",
"CONCLUSIONS"
] | [
0,
0
] | ## CONCLUSIONS |
14734469 | [
"BRAF",
"mutations",
"are",
"frequently",
"present",
"in",
"sporadic",
"colorectal",
"cancer",
"with",
"methylated",
"hMLH1",
"mutations",
" ",
"(P",
"<",
"0.00001).",
"Sixteen",
"of",
"17",
"mutations",
"were",
"at",
"residue",
"599",
"(V599E).",
"A",
"BRAF",
"mutation",
"was",
"also",
"identified",
"at",
"residue",
"463",
"(G463V)",
"in",
"one",
"cell",
"line.",
"In",
"addition,",
"BRAF",
"mutations",
"were",
"not",
"found",
"in",
"any",
"cancers",
"or",
"cell",
"lines",
"with",
"K-ras",
"mutations.",
"In",
"20",
"MSI+",
"cancers",
"from",
"HNPCC",
"patients,",
"however,",
"BRAF",
"mutations",
"were",
"not",
"detectable,",
"including",
"a",
"subset",
"of",
"9",
"tumors",
"with",
"negative",
"hMLH1",
"immunostaining",
"and",
"methylated",
"hMLH1."
] | [
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
] | BRAF mutations are frequently present in sporadic colorectal cancer with methylated hMLH1 mutations (P < 0.00001). Sixteen of 17 mutations were at residue 599 (V599E). A BRAF mutation was also identified at residue 463 (G463V) in one cell line. In addition, BRAF mutations were not found in any cancers or cell lines with K-ras mutations. In 20 MSI+ cancers from HNPCC patients, however, BRAF mutations were not detectable, including a subset of 9 tumors with negative hMLH1 immunostaining and methylated hMLH1. |
17350669 | [] | [] | |
19706845 | [
"Sixteen",
"tag",
"SNPs",
"ADH1B",
",",
"ALDH2,",
"and",
"CYP2E1,",
"and",
"to",
"evaluate",
"the",
"association",
"between",
"these",
"tagSNPs",
"and",
"colorectal",
"cancer",
"(CRC)",
"in",
"a",
"southwestern",
"Chinese",
"population."
] | [
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
] | Sixteen tag SNPs ADH1B , ALDH2, and CYP2E1, and to evaluate the association between these tagSNPs and colorectal cancer (CRC) in a southwestern Chinese population. |
9476377 | [
"The",
"present",
"paper",
"is",
"the",
"first",
"part",
"of",
"an",
"analysis",
"of",
"37",
"different",
"Czech",
"families",
"with",
"83",
"members",
"affected",
"by",
"FAP.",
"Our",
"goal",
"is",
"to",
"identify",
"the",
"mutation",
" ",
"characteristic",
"for",
"each",
"family",
"for",
"early",
"diagnosis",
"of",
"FAP.",
"We",
"screened",
"clinically",
"manifest",
"representatives",
"of",
"nine",
"families",
"for",
"mutations",
"in",
"exon",
"15",
"of",
"the",
"APC",
"gene.",
"First,",
"we",
"searched",
"for",
"the",
"mutation",
"hot",
"spots",
"(codons",
"1061",
"and",
"1309,",
"respectively)",
"and",
"later",
"for",
"the",
"entire",
"exon",
"15.",
"Denatured",
"gradient",
"gel",
"electrophoresis",
"(DGGE)",
"of",
"amplified",
"regions",
"ov",
"exon",
"15",
"has",
"been",
"used",
"to",
"identify",
"DNA",
"sequence",
"variations",
"followed",
"by",
"sequencing",
"verification.",
"In",
"seven",
"patients,",
"seven",
"different",
"mutations",
"in",
"exon",
"15",
"of",
"APC",
"gene,",
"four",
"deletion",
"mutants",
"(5-base",
"deletions",
"in",
"codons",
"1061",
"and",
"1309",
"codons",
"1061",
" ",
"and",
"1309,",
"1-base",
"deletion",
"in",
"codons",
"759",
" ",
"and",
"7-base",
"deletion",
"combined",
"with",
"a",
"2-base",
"insertion",
"in",
"codon",
"712",
"),",
"one",
"insertion",
"mutation",
"(1-base/A/insertion",
"in",
"codon",
"1554",
")",
"and",
"two",
"point",
"mutations",
"(C",
"to",
"T",
"and",
"C",
"to",
"A",
"substitutions",
"in",
"codons",
"737",
"and",
"935",
"codons",
"737",
" ",
"and",
"935,",
"respectively,",
"in",
"both",
"cases",
"leading",
"to",
"formation",
"of",
"stop",
"codons)",
"have",
"been",
"found."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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,
7,
8,
0,
0,
0,
0,
0,
0,
7,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
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,
7,
7,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] | The present paper is the first part of an analysis of 37 different Czech families with 83 members affected by FAP. Our goal is to identify the mutation characteristic for each family for early diagnosis of FAP. We screened clinically manifest representatives of nine families for mutations in exon 15 of the APC gene. First, we searched for the mutation hot spots (codons 1061 and 1309, respectively) and later for the entire exon 15. Denatured gradient gel electrophoresis (DGGE) of amplified regions ov exon 15 has been used to identify DNA sequence variations followed by sequencing verification. In seven patients, seven different mutations in exon 15 of APC gene, four deletion mutants (5-base deletions in codons 1061 and 1309 codons 1061 and 1309, 1-base deletion in codons 759 and 7-base deletion combined with a 2-base insertion in codon 712 ), one insertion mutation (1-base/A/insertion in codon 1554 ) and two point mutations (C to T and C to A substitutions in codons 737 and 935 codons 737 and 935, respectively, in both cases leading to formation of stop codons) have been found. |
25840688 | [] | [] | |
23497483 | [
"##",
"RESULTS"
] | [
0,
0
] | ## RESULTS |