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9731891
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
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25029911
[ "As", "a", "novel", "candidate", "metastasis", "suppressor", "gene,", "Nasopharyngeal", "carcinoma-associated", "gene", "6", "(NGX6)", "is", "involved", "in", "cellular", "growth,", "cell", "cycle", "progression", "and", "tumor", "angiogenesis.", "Previous", "studies", "have", "shown", "that", "NGX6", "gene", "is", "down-regulated", "in", "colorectal", "cancer", "(CRC).", "However,", "little", "is", "known", "about", "its", "transcriptional", "regulation." ]
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As a novel candidate metastasis suppressor gene, Nasopharyngeal carcinoma-associated gene 6 (NGX6) is involved in cellular growth, cell cycle progression and tumor angiogenesis. Previous studies have shown that NGX6 gene is down-regulated in colorectal cancer (CRC). However, little is known about its transcriptional regulation.
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14734469
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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22810479
[ ":", "The", "K-ras", "gene", "is", "one", "of", "the", "commonly", "mutated", "oncogenes", "associated", "with", "colorectal", "cancer.", "However,", "its", "prognostic", "significance", "for", "patients", "with", "colorectal", "cancer", "remains", "inconclusive." ]
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: The K-ras gene is one of the commonly mutated oncogenes associated with colorectal cancer. However, its prognostic significance for patients with colorectal cancer remains inconclusive.
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17007003
[ "Collision", "tumor", "of", "the", "rectum:", "a", "case", "report", "of", "metastatic", "gastric", "adenocarcinoma", "plus", "primary", "rectal", "adenocarcinoma." ]
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Collision tumor of the rectum: a case report of metastatic gastric adenocarcinoma plus primary rectal adenocarcinoma.
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22810479
[ ":", "The", "K-ras", "gene", "is", "one", "of", "the", "commonly", "mutated", "oncogenes", "associated", "with", "colorectal", "cancer.", "However,", "its", "prognostic", "significance", "for", "patients", "with", "colorectal", "cancer", "remains", "inconclusive." ]
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: The K-ras gene is one of the commonly mutated oncogenes associated with colorectal cancer. However, its prognostic significance for patients with colorectal cancer remains inconclusive.
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26416897
[ "TBK1", "rs7486100", "was", "significantly", "associated", "with", "overall", "survival", "in", "95", "KRAS", "wild-type", "patients", "of", "TRIBE", "cohort", "in", "univariate", "analysis", "and", "had", "a", "strong", "trend", "in", "multivariable", "analysis;", "furthermore,", "the", "association", "of", "the", "T", "allele", "was", "observed", "for", "progression-free", "survival", "(PFS)", "in", "both", "univariate", "and", "multivariable", "analyses", "in", "FIRE3-bevacizumab", "but", "not", "cetuximab", "cohort.", "CCL2", "rs4586", "NFKB1", ",", "TBK1,", "CCL18,", "and", "IRF3)", "were", "tested", "for", "associations", "with", "clinical", "outcomes", "in", "a", "discovery", "cohort", "of", "228", "participants", "in", "TRIBE", "trial", "(NCT00719797),", "then", "validated", "in", "248", "KRAS", "exon2", "(KRAS)", "wild-type", "participants", "in", "FIRE3", "trial", "(NCT00433927).", "FIRE3-cetuximab", "cohort", "served", "as", "a", "negative", "control." ]
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TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586 NFKB1 , TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control.
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11766074
[ "Attenuated", "familial", "adenomatous", "polyposis", "associated", "with", "advanced", "rectal", "cancer", "in", "a", "16-year-old", "boy:", "report", "of", "a", "case." ]
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Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case.
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15702478
[ "Gene", "mutations", "in", "APC,", "K-ras,", "and", "p53", "are", "thought", "to", "be", "essential", "events", "for", "colorectal", "cancer", "development.", "Recent", "data", "seem", "to", "indicate", "that", "K-ras", "and", "p53", "mutations", "rarely", "co-exist", "in", "the", "same", "tumor,", "indicating", "that", "these", "alterations", "do", "not", "represent", "a", "synergistic", "evolutionary", "pathway.", "Moreover,", "an", "inverse", "relation", "between", "K-ras", "gene", "activation", "K-ras", ",", "and", "BRAF", "genes", "in", "colorectal", "cancer", "progression." ]
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Gene mutations in APC, K-ras, and p53 are thought to be essential events for colorectal cancer development. Recent data seem to indicate that K-ras and p53 mutations rarely co-exist in the same tumor, indicating that these alterations do not represent a synergistic evolutionary pathway. Moreover, an inverse relation between K-ras gene activation K-ras , and BRAF genes in colorectal cancer progression.
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16426918
[]
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12534642
[ "##", "METHODS" ]
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## METHODS
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9609758
[ "Sporadic", "colorectal", "cancers", "do", "not", "show", "an", "absence", "or", "a", "presence", "of", "mutated", "TGF-beta", "receptors", "that", "could", "explain", "a", "resistance", "to", "TGF-beta", "mutated", "transforming", "growth", "factor", "beta", "receptors", " ", "in", "normal", "human", "colon", "and", "sporadic", "adenocarcinomas.", "\n\n\n", "##", "BACKGROUND", "&", "AIMS" ]
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Sporadic colorectal cancers do not show an absence or a presence of mutated TGF-beta receptors that could explain a resistance to TGF-beta mutated transforming growth factor beta receptors in normal human colon and sporadic adenocarcinomas. ## BACKGROUND & AIMS
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20198339
[]
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24568449
[ "##", "CONCLUSIONS" ]
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9731891
[ "One", "hundred", "and", "twenty-five", "cases", "of", "sporadic", "colon", "carcinoma", "(50", "in", "the", "right", "colon", "and", "75", "in", "the", "left", "colon", "in", "patients", "with", "no", "family", "history", "of", "colon", "carcinoma)", "were", "studied.", "Status", "of", "the", "p53", "gene", "was", "assessed", "by", "polymerase", "chain", "reaction", "(PCR),", "single", "strand", "conformation", "polymorphism,", "and", "sequencing", "at", "exons", "5-8.", "Microsatellite", "instability", "was", "analyzed", "with", "five", "microsatellite", "markers", "at", "chromosome", "18.", "The", "mismatch", "repair", "genes", "hMLH1", "and", "hMSH2", "were", "studied", "in", "tumors", "found", "to", "have", "microsatellite", "instability", "by", "PCR", "and", "sequencing." ]
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One hundred and twenty-five cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing.
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24225759
[ "##", "RESULTS" ]
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## RESULTS
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22899730
[ "##", "RESULTS" ]
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## RESULTS
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24568449
[ "Associations", "of", "single", "nucleotide", "polymorphisms", "in", "miR-146a,", "miR-196a,", "miR-149", "and", "miR-499", "with", "colorectal", "cancer", "susceptibility.", "\n\n\n", "##", "BACKGROUND" ]
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Associations of single nucleotide polymorphisms in miR-146a, miR-196a, miR-149 and miR-499 with colorectal cancer susceptibility. ## BACKGROUND
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19276868
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
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22899730
[ "Among", "1,980", "cases", "tested,", "12%", "were", "BRAF", "c.1799T>A", "(p.V600E)", "mutation-positive", "(n", "=", "247).", "BRAF-mutated", "CRC", "was", "associated", "with", "poorer", "disease-specific", "survival", "adjusting", "for", "age,", "sex,", "time", "from", "diagnosis", "to", "enrollment,", "stage,", "and", "MSI", "status", "(HR,", "1.43;", "95%", "CI,", "1.05-1.95).", "This", "association", "was", "limited", "to", "cases", "diagnosed", "at", "ages", "<50", "(HR,", "3.06;", "95%", "CI,", "1.70-5.52)", "and", "was", "not", "evident", "in", "cases", "with", "MSI-high", "tumors", "(HR,", "0.94;", "95%", "CI,", "0.44-2.03).", "Associations", "with", "overall", "survival", "were", "similar." ]
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Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation-positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70-5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44-2.03). Associations with overall survival were similar.
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22545919
[ "Two", "SNPs", "SNPs", ")", "in", "genes", "from", "the", "oxidative", "phosphorylation", "chain", "with", "survival", "and", "disease", "prognosis", "in", "613", "CRC", "patients", "from", "Northern", "Germany", "(PopGen", "cohort)." ]
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Two SNPs SNPs ) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort).
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14645426
[ "Toward", "new", "strategies", "to", "select", "young", "endometrial", "cancer", "patients", "for", "mismatch", "repair", "gene", "mutation", "analysis.", "\n\n\n", "##", "PURPOSE" ]
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Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis. ## PURPOSE
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9731891
[ "Left", "and", "right", "colon", "carcinomas", "can", "display", "different", "clinical,", "pathologic,", "and", "genetic", "characteristics.", "The", "purpose", "of", "this", "study", "was", "to", "characterize", "multiple", "molecular", "genetic", "alterations", "in", "sporadic", "colon", "carcinoma", "and", "to", "correlate", "them", "with", "the", "location", "of", "the", "tumors", "and", "with", "lymph", "node", "metastasis." ]
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Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis.
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25374237
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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26302849
[]
[]
[ 2, 3 ]
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[ 1, 1 ]
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23132392
[ "Somatic", "MED12", "exon", "2", "mutations", "mutations", " ", "in", "other", "tumour", "types." ]
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Somatic MED12 exon 2 mutations mutations in other tumour types.
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8431846
[ "These", "results", "suggest", "that", "the", "development", "of", "hyperplastic", "polyps", "and", "carcinoma", "of", "the", "rectum", "results", "from", "the", "allelic", "loss", "in", "chromosome", "3p", "deletion", " ", "often", "is", "found", "for", "chromosomes", "5,", "17,", "and", "18,", "on", "which", "tumor", "suppressor", "genes", "are", "located.", "Furthermore,", "loss", " ", "of", "the", "alleles", "of", "loci", "on", "chromosome", "3", " ", "has", "been", "reported", "in", "renal", "cell", "carcinoma,", "small", "cell", "lung", "carcinoma,", "and", "mixed", "salivary", "gland", "tumor", "in", "hereditary", "and", "sporadic", "cases.", "These", "data", "support", "the", "concept", "of", "a", "recessive", "mechanism", "for", "the", "development", "of", "human", "tumors." ]
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These results suggest that the development of hyperplastic polyps and carcinoma of the rectum results from the allelic loss in chromosome 3p deletion often is found for chromosomes 5, 17, and 18, on which tumor suppressor genes are located. Furthermore, loss of the alleles of loci on chromosome 3 has been reported in renal cell carcinoma, small cell lung carcinoma, and mixed salivary gland tumor in hereditary and sporadic cases. These data support the concept of a recessive mechanism for the development of human tumors.
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12702972
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The gastrointestinal epithelium is known to undergo constant and rapid renewal resulting in millions of cells being shed into the fecal stream every day. The conventional wisdom was that these cells disintegrate upon exfoliation and will not survive the transit through the intestinal tract. In 1990, we (P.N.) made the discovery that a significant number of these cells remain intact and viable and that they can be isolated. The implications of this important discovery became apparent when we demonstrated that these cells are exclusively of colonic origin, are anatomically representative of the entire colon, and can be used for clinical investigations of disease processes. The term coprocytobiology (CCB) was coined to encompass the broad range of applications of this new technology. The somatic cell sampling and recovery (SCSR) process involves the isolation of exfoliated colonocytes from a small sample of stool ( approximately 1 g) collected and transported in a unique medium at ambient temperature, providing cells for the detection of a number of biomarkers of disease propensity. These exfoliated colonocytes express cytokeratins indicating epithelial lineage as well as colon-specific antigen. Over the years, the study of exfoliated colonocytes has provided striking new insights into the biology of colon cancer and inflammatory bowel disease, including detection of p53 gene mutations, reverse transcriptase polymerase chain reaction amplification, and identification of CD44 splice variants, neoplasia-associated specific binding of plant lectins, and expression of COX-2, the inducible form of cyclooxygenase. The functional diversity of cells isolated by SCSR is revealed by the demonstration of cell surface markers such as secretory component, IgA, and IgG on the one hand and the amplification and cloning of the human insulin receptor and the expression of the multidrug resistance gene mdr-1 p53 gene mutations , reverse transcriptase polymerase chain reaction amplification, and identification of CD44 splice variants , neoplasia-associated specific binding of plant lectins , and expression of COX-2, the inducible form of cyclooxygenase COX-2 , the inducible form of cyclooxygenase. The functional diversity of cells isolated by SCSR is revealed by the demonstration of cell surface markers such as secretory component, IgA , and IgG on the one hand and the amplification and cloning of the human insulin receptor and the expression of the multidrug resistance gene mdr-1 on the other hand. This review portrays the immense potential of CCB as a powerful tool for investigating the pathophysiology of disease, identifying genetic variants in pharmacogenetics, assessment of mucosal immunity, and several other applications that use somatic cells.
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26925673
[ "##", "MATERIALS", "AND", "METHODS" ]
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## MATERIALS AND METHODS
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8709782
[ "##", "FINDINGS" ]
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## FINDINGS
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9609758
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Thirty-three sporadic colorectal cancers and 20 normal colonic tissues were explored by immunohistochemistry for the expression of type I and type II TGF-beta receptors. Eighteen tumor and 20 normal samples were used for radioactive thermocycling and sequencing of the two microsatellite-like regions of the type II receptor.
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1319833
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We have previously observed that the frequency of loss of heterozygosity (LOH) on chromosome 18q was low in adenomas and intramucosal carcinomas, whereas invasive carcinomas exhibited a high frequency in familial adenomatous polyposis patients (M. Miyaki et al., Cancer Res., 50: 7166-7173, 1990). In the present study, LOH at the DCC locus on chromosome 18q and the expression of DCC gene into mRNA were analyzed in colorectal tumors with distinct histopathological types. The carcinomas that showed 18q LOH also lost the DCC locus. The expression of DCC gene into mRNA was examined at the level of 233-base pair fragments of nucleotide 986-1218 in DCC complementary DNA. In a moderate-to-severe adenoma, 5 carcinoma-in-adenomas, and 4 intramucosal carcinomas, the level of expression was as high as in normal colorectal mucosa, whereas it was greatly reduced or not detectable in most (13 of 16) invasive carcinomas. Among these invasive carcinomas, 7 of 11 showed 18q LOH, but 4 showed no LOH. These results suggest that the DCC gene is included in the allelic deletion on chromosome 18q nucleotide 986-1218 in DCC complementary DNA. In a moderate-to-severe adenoma, 5 carcinoma-in-adenomas, and 4 intramucosal carcinomas, the level of expression was as high as in normal colorectal mucosa, whereas it was greatly reduced or not detectable in most (13 of 16) invasive carcinomas. Among these invasive carcinomas, 7 of 11 showed 18q LOH, but 4 showed no LOH. These results suggest that the DCC gene is included in the allelic deletion on chromosome 18q, and that the progression of colorectal carcinoma from early stage to advanced stage accompanies the inactivation LOH at the DCC locus on chromosome 18q and the expression of DCC gene into mRNA were analyzed in colorectal tumors with distinct histopathological types. The carcinomas that showed 18q LOH also lost the DCC locus. The expression of DCC gene into mRNA was examined at the level of 233-base pair fragments of nucleotide 986-1218 in DCC complementary DNA. In a moderate-to-severe adenoma, 5 carcinoma-in-adenomas, and 4 intramucosal carcinomas, the level of expression was as high as in normal colorectal mucosa, whereas it was greatly reduced or not detectable in most (13 of 16) invasive carcinomas. Among these invasive carcinomas, 7 of 11 showed 18q LOH, but 4 showed no LOH. These results suggest that the DCC gene is included in the allelic deletion on chromosome 18q, and that the progression of colorectal carcinoma from early stage to advanced stage accompanies the inactivation of the DCC DCC gene into mRNA was examined at the level of 233-base pair fragments of nucleotide 986-1218 in DCC complementary DNA. In a moderate-to-severe adenoma, 5 carcinoma-in-adenomas, and 4 intramucosal carcinomas, the level of expression was as high as in normal colorectal mucosa, whereas it was greatly reduced or not detectable in most (13 of 16) invasive carcinomas. Among these invasive carcinomas, 7 of 11 showed 18q LOH, but 4 showed no LOH. These results suggest that the DCC gene is included in the allelic deletion on chromosome 18q, and that the progression of colorectal carcinoma from early stage to advanced stage accompanies the inactivation of the DCC gene through LOH DCC complementary DNA. In a moderate-to-severe adenoma, 5 carcinoma-in-adenomas, and 4 intramucosal carcinomas, the level of expression was as high as in normal colorectal mucosa, whereas it was greatly reduced or not detectable in most (13 of 16) invasive carcinomas. Among these invasive carcinomas, 7 of 11 showed 18q LOH 18q LOH, but 4 showed no LOH . These results suggest that the DCC gene is included in the allelic deletion DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial adenomatous polyposis patients.
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25029911
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These results demonstrate that Egr-1 regulates NGX6 Egr-1 regulates the transcription of NGX6 gene through a Sp1/Egr-1 overlapping site in the promoter. ## BACKGROUND
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23797718
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9841584
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## OBJECTIVE
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22899730
[ "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." ]
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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.
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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." ]
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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.
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14966376
[ "Colorectal", "cancer", "has", "become", "the", "third", "leading", "cause", "of", "death", "from", "cancer", "in", "Taiwan.", "Familial", "adenomatous", "polyposis", "(FAP)", "is", "an", "autosomal", "dominant", "inherited", "disease", "characterized", "by", "the", "presence", "of", "multiple", "adenomatous", "polyps", "in", "the", "colon", "and", "rectum.", "The", "gene", "responsible", "for", "FAP", "(APC)", "was", "cloned", "in", "1991.", "Extensive", "analyses", "of", "the", "mutation", "spectra", "in", "FAP", "kindreds", "have", "been", "performed", "in", "different", "countries,", "but", "the", "results", "have", "been", "highly", "variable", "(30-80%).", "In", "this", "study,", "we", "used", "denaturing", "high-performance", "liquid", "chromatography", "(DHPLC)", "followed", "by", "automatic", "sequencing", "in", "an", "effort", "to", "establish", "the", "mutation", "spectrum", "of", "APC", "from", "DNA", "of", "peripheral", "blood", "cells.", "Among", "the", "6", "FAP", "probands", "analyzed,", "mutations", "were", "detected", "in", "3", "(50%),", "2", "of", "which", "were", "novel.", "The", "first", "novel", "mutation", " ", "was", "at", "codon", "2166,", "with", "a", "C", "to", "T", "transition,", "resulting", "in", "a", "stop", "codon.", "The", "second", "novel", "mutation", " ", "was", "at", "codon", "1971,", "with", "a", "C", "to", "G", "transversion,", "resulting", "in", "an", "amino", "acid", "change", "from", "serine", "to", "cysteine.", "The", "third", "mutation", "involved", "an", "A", "insertion", "in", "the", "sequence", "of", "-AAAAAA-", "at", "codons", "1554-1556", "mutation", " ", "involved", "an", "A", "insertion", "in", "the", "sequence", "of", "-AAAAAA-", "at", "codons", "1554-1556,", "which", "created", "a", "downstream", "stop", "codon", "(codon", "1558).", "This", "study", "is", "the", "first", "to", "report", "mutation", "APC", ")", "was", "cloned", "in", "1991.", "Extensive", "analyses", "of", "the", "mutation", "spectra", "in", "FAP", "kindreds", "have", "been", "performed", "in", "different", "countries,", "but", "the", "results", "have", "been", "highly", "variable", "(30-80%).", "In", "this", "study,", "we", "used", "denaturing", "high-performance", "liquid", "chromatography", "(DHPLC)", "followed", "by", "automatic", "sequencing", "in", "an", "effort", "to", "establish", "the", "mutation", "spectrum", "of", "APC", "APC", " ", "gene", "in", "Taiwanese", "familial", "adenomatous", "polyposis." ]
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Colorectal cancer has become the third leading cause of death from cancer in Taiwan. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of multiple adenomatous polyps in the colon and rectum. The gene responsible for FAP (APC) was cloned in 1991. Extensive analyses of the mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30-80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166, with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554-1556 mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554-1556, which created a downstream stop codon (codon 1558). This study is the first to report mutation APC ) was cloned in 1991. Extensive analyses of the mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30-80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC APC gene in Taiwanese familial adenomatous polyposis.
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14645426
[ "In", "23%", "of", "the", "young", "endometrial", "cancer", "patients", "with", "at", "least", "one", "first-degree", "relative", "with", "an", "HNPCC-related", "cancer,", "an", "MMR", "gene", "mutation", "was", "detected.", "Therefore,", "presence", "of", "an", "HNPCC-related", "cancer", "in", "a", "first-degree", "relative", "seems", "to", "be", "an", "important", "selection", "criterion", "for", "mutation", "mutation", "mutations", " ", "in", "endometrial", "cancer", "patients", "who", "were", "diagnosed", "at", "less", "than", "50", "years", "of", "age;", "to", "relate", "the", "presence", "of", "mutations", "to", "family", "history,", "histopathologic", "data,", "presence", "of", "tumor", "microsatellite", "instability", "(MSI),", "and", "immunostaining;", "and", "to", "formulate", "criteria", "for", "genetic", "testing", "in", "these", "patients." ]
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In 23% of the young endometrial cancer patients with at least one first-degree relative with an HNPCC-related cancer, an MMR gene mutation was detected. Therefore, presence of an HNPCC-related cancer in a first-degree relative seems to be an important selection criterion for mutation mutation mutations in endometrial cancer patients who were diagnosed at less than 50 years of age; to relate the presence of mutations to family history, histopathologic data, presence of tumor microsatellite instability (MSI), and immunostaining; and to formulate criteria for genetic testing in these patients.
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20646601
[ "A", "total", "of", "208", "colorectal", "cancer", "tissue", "samples", "were", "collected", "from", "September", "2008", "to", "February", "2009.", "DNA", "was", "extracted", "with", "a", "genomic", "DNA", "miniprep", "kit.", "Then", "PCR", "was", "performed", "with", "the", "designed", "primers", "and", "the", "product", "directly", "sequenced", "by", "the", "Sanger", "method.", "Then", "the", "associations", "between", "K-ras", " ", "mutation", "status", "and", "clinicopathological", "characteristics", "in", "colorectal", "cancer", "were", "analyzed." ]
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A total of 208 colorectal cancer tissue samples were collected from September 2008 to February 2009. DNA was extracted with a genomic DNA miniprep kit. Then PCR was performed with the designed primers and the product directly sequenced by the Sanger method. Then the associations between K-ras mutation status and clinicopathological characteristics in colorectal cancer were analyzed.
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12534642
[ "(i)", "CYP1A2", "polymorphisms", "are", "in", "linkage", "disequilibrium.", "Therefore,", "only", "-164A-->C", "(CYP1A2*1F)", "and", "-2464T-->delT", "(", "CYP1A2*1D", ")", "need", "to", "be", "analysed", "in", "the", "routine", "assessment", "of", "CYP1A2", "genotype;", "(ii)", "in", "vivo", "CYP1A2", "activity", "is", "lower", "in", "colorectal", "cancer", "patients", "than", "in", "controls,", "and", "(iii)", "CYP1A2", "-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." ]
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(i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only -164A-->C (CYP1A2*1F) and -2464T-->delT ( CYP1A2*1D ) need to be analysed in the routine assessment of CYP1A2 genotype; (ii) in vivo CYP1A2 activity is lower in colorectal cancer patients than in controls, and (iii) CYP1A2 -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.
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20198339
[ "MUC2", "is", "a", "major", "secretory", "mucin", "normally", "expressed", "by", "goblet", "cells", "of", "the", "intestine,", "but", "is", "aberrantly", "expressed", "in", "colonic", "neoplasia.", "Bile", "acids", "have", "been", "implicated", "in", "colorectal", "carcinogenesis", "and,", "therefore,", "we", "sought", "to", "determine", "the", "effects", "of", "bile", "acids", "on", "MUC2", "expression", "and", "regulation", "in", "colon", "cancer", "cells.", "Since", "deoxycholic", "acid", "(DCA),", "a", "secondary", "bile", "acid,", "has", "been", "reported", "to", "be", "a", "potent", "mucin", "secretagogue", "and", "tumor", "promoter,", "DCA-treated", "HM3", "colon", "cancer", "cells", "were", "analyzed", "using", "promoter-reporter", "assays", "of", "the", "5'", "flanking", "region", "of", "the", "MUC2", "gene.", "Chemical", "inhibitors,", "mutant", "reporter", "constructs", "and", "EMSA", "showed", "that", "DCA", "upregulates", "MUC2", "transcription", "via", "multiple", "pathways", "involving", "activation", "of", "EGFR/PKC/Ras/Raf-1/MEK1/ERK/CREB,", "PI3/Akt/IkappaB/NF-kappaB", "and", "p38/MSK1/CREB", "while", "DCA", "induced", "MUC2", "transcription", "is", "inhibited", "by", "JNK/", "c-Jun", "Akt", "AP-1", "p38", "/MSK1/CREB", "pathways", "and", "negative", "JNK/c-Jun/AP-1", "pathway." ]
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MUC2 is a major secretory mucin normally expressed by goblet cells of the intestine, but is aberrantly expressed in colonic neoplasia. Bile acids have been implicated in colorectal carcinogenesis and, therefore, we sought to determine the effects of bile acids on MUC2 expression and regulation in colon cancer cells. Since deoxycholic acid (DCA), a secondary bile acid, has been reported to be a potent mucin secretagogue and tumor promoter, DCA-treated HM3 colon cancer cells were analyzed using promoter-reporter assays of the 5' flanking region of the MUC2 gene. Chemical inhibitors, mutant reporter constructs and EMSA showed that DCA upregulates MUC2 transcription via multiple pathways involving activation of EGFR/PKC/Ras/Raf-1/MEK1/ERK/CREB, PI3/Akt/IkappaB/NF-kappaB and p38/MSK1/CREB while DCA induced MUC2 transcription is inhibited by JNK/ c-Jun Akt AP-1 p38 /MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway.
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15946795
[ "Little", "is", "known", "about", "genetic", "risk", "factors", "for", "colorectal", "cancer.", "We", "assessed", "the", "association", "between", "polymorphisms", "in", "two", "genes", "involved", "in", "DNA", "repair", "of", "oxidative", "stress,", "GPX", "and", "OGG1,", "and", "risk", "of", "colorectal", "carcinoma", "or", "adenomas.", "We", "studied", "166", "cases", "with", "adenocarcinoma,", "974", "with", "adenomas", "and", "397", "controls", "recruited", "from", "the", "Norwegian", "cohort", "NORCCAP.", "No", "associations", "were", "found", "between", "the", "polymorphism", "GPX", "Pro198Leu", "and", "risk", "of", "colorectal", "adenomas", "or", "carcinomas.", "Carriers", "of", "the", "variant", "allele", "OGG1", "Ser326Cys", "GPX", " ", "Pro198Leu", " ", "and", "risk", "of", "colorectal", "adenomas", "or", "carcinomas.", "Carriers", "of", "the", "variant", "allele", "OGG1", "GPX", " ", "Pro198Leu", " ", "and", "OGG1", " ", "Ser326Cys", "polymorphisms", "and", "risk", "of", "development", "of", "colorectal", "adenomas", "and", "colorectal", "cancer." ]
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Little is known about genetic risk factors for colorectal cancer. We assessed the association between polymorphisms in two genes involved in DNA repair of oxidative stress, GPX and OGG1, and risk of colorectal carcinoma or adenomas. We studied 166 cases with adenocarcinoma, 974 with adenomas and 397 controls recruited from the Norwegian cohort NORCCAP. No associations were found between the polymorphism GPX Pro198Leu and risk of colorectal adenomas or carcinomas. Carriers of the variant allele OGG1 Ser326Cys GPX Pro198Leu and risk of colorectal adenomas or carcinomas. Carriers of the variant allele OGG1 GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer.
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26302849
[ "The", "genotype", "\"A/T\"", "of", "rs12413624", " ", "in", "PRLHR", "gene", "was", "associated", "with", "a", "decreased", "risk", "of", "colorectal", "cancer", "in", "allele", "model", "analysis", "[odds", "ratio", "(OR)", " ", "=", " ", "0.81;", "95%", "confidence", "interval", "(CI)", " ", "=", " ", "0.68-0.97;", "p", " ", "=", " ", "0.018]", "and", "log-additive", "model", "analysis", "(OR", " ", "=", " ", "0.81;", "95%", "CI", " ", "=", " ", "0.66-0.98;", "p", " ", "=", " ", "0.032).", "The", "genotype", "\"A/G\"", "of", "rs1665650", "PRLHR", " ", "gene", "was", "associated", "with", "a", "decreased", "risk", "of", "colorectal", "cancer", "in", "allele", "model", "analysis", "[odds", "ratio", "(OR)", " ", "=", " ", "0.81;", "95%", "confidence", "interval", "(CI)", " ", "=", " ", "0.68-0.97;", "p", " ", "=", " ", "0.018]", "and", "log-additive", "model", "analysis", "(OR", " ", "=", " ", "0.81;", "95%", "CI", " ", "=", " ", "0.66-0.98;", "p", " ", "=", " ", "0.032).", "The", "genotype", "\"A/G\"", "of", "rs1665650", "in", "HSPA12A", "gene", "was", "associated", "with", "a", "decreased", "risk", "of", "gastric", "cancer", "in", "overdominant", "model", "analysis", "(OR", " ", "=", " ", "0.77;", "95%", "CI", " ", "=", " ", "0.60-0.99;", "p", " ", "=", " ", "0.038)." ]
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The genotype "A/T" of rs12413624 in PRLHR gene was associated with a decreased risk of colorectal cancer in allele model analysis [odds ratio (OR)   =   0.81; 95% confidence interval (CI)   =   0.68-0.97; p   =   0.018] and log-additive model analysis (OR   =   0.81; 95% CI   =   0.66-0.98; p   =   0.032). The genotype "A/G" of rs1665650 PRLHR gene was associated with a decreased risk of colorectal cancer in allele model analysis [odds ratio (OR)   =   0.81; 95% confidence interval (CI)   =   0.68-0.97; p   =   0.018] and log-additive model analysis (OR   =   0.81; 95% CI   =   0.66-0.98; p   =   0.032). The genotype "A/G" of rs1665650 in HSPA12A gene was associated with a decreased risk of gastric cancer in overdominant model analysis (OR   =   0.77; 95% CI   =   0.60-0.99; p   =   0.038).
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17454882
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A simple explanation for the combined findings may be that all selected families had a similar tendency to produce adenomas, while mutation carriers more frequently demonstrated dysplasia/cancer in the adenomas. The low annual incidence rates for CRC indicated that the removal of adenomas may have prevented cancers.
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22895193
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Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations TCF7L2 , chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3 . Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM . Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin copy-number alterations . We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC RSPO3 R-spondin fusions in colon cancer.
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26925673
[ "Impact", "of", "Cellular", "Genetic", "Make-up", "on", "Colorectal", "Cancer", "Cell", "Lines", "Response", "to", "Ellagic", "Acid:", "Implications", "of", "Small", "Interfering", "RNA.", "\n\n\n", "##", "BACKGROUND" ]
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Impact of Cellular Genetic Make-up on Colorectal Cancer Cell Lines Response to Ellagic Acid: Implications of Small Interfering RNA. ## BACKGROUND
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22810479
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: To derive a more precise estimation of the prognostic significance of K-ras gene mutations, a systematic review and meta-analysis were performed.
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23132392
[ "Five", "somatic", "alterations", "were", "observed:", "three", "in", "uterine", "leiomyosarcomas", "(3/41,", "7%;", "Gly44Ser,", "Ala38_Leu39ins7,", "Glu35_Leu36delinsVal),", "and", "two", "in", "CRC", "(2/392,", "0.5%;", "Gly44Cys,", "Ala67Val)." ]
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Five somatic alterations were observed: three in uterine leiomyosarcomas (3/41, 7%; Gly44Ser, Ala38_Leu39ins7, Glu35_Leu36delinsVal), and two in CRC (2/392, 0.5%; Gly44Cys, Ala67Val).
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9841584
[ "Decision", "about", "a", "cancer", "prevention", "strategy", "at", "the", "time", "of", "a", "positive", "result", "on", "genetic", "testing." ]
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Decision about a cancer prevention strategy at the time of a positive result on genetic testing.
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22396040
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The associations between four common genetic polymorphisms of transforming growth factor-β1 (TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers vs. TT for -509 C > T, 1.03 for C carriers vs. TT for +869 T > C, 1.09 for C carriers vs. GG for +915 G > C, and 1.19 for A carriers vs. GG for 800 G > A). However, C allele of TGF-β1 -509 C > T and A allele of -800 G > A were associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was 1.23 (0.99-1.52) for CC vs. TT for -509 C > T and 6.64 (3.46-12.72) for A carriers vs. GG. The positive association between -509 C allele and risk of CRC was more obvious when subgroup analyses were conducted for population-based and large sample-sized studies as well as Caucasians. In contrast, we did not observed any associations between TGF-β1 -509 C > T and 6.64 (3.46-12.72) for A carriers vs. GG. The positive association between -509 C allele and risk of CRC was more obvious when subgroup analyses were conducted for population-based and large sample-sized studies as well as Caucasians. In contrast, we did not observed any associations between TGF-β1   +869 T > C, +915 G > C +869 T > C , +915 G > C, and risk of CRC. This study indicated that C allele of TGF-β1 -509 C > T TGF-β1 -509 C > T and A allele of -800 G > A TGF-β1 genetic polymorphisms and risk of colorectal tumor.
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22899730
[ "##", "IMPACT" ]
[ 0, 0 ]
## IMPACT
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12534642
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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19276868
[ "UA62784", "is", "a", "small", "molecule", "that", "selectively", "kills", "DPC4-deficient", "cancer", "cells.", "Its", "potent", "activity", "and", "relatively", "low", "molecular", "weight", "make", "it", "a", "decent", "candidate", "for", "further", "lead", "optimization." ]
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UA62784 is a small molecule that selectively kills DPC4-deficient cancer cells. Its potent activity and relatively low molecular weight make it a decent candidate for further lead optimization.
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25029911
[ "##", "CONCLUSION" ]
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## CONCLUSION
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14734469
[ "BRAF", "mutation", "is", "frequently", "present", "in", "sporadic", "colorectal", "cancer", "with", "methylated", "hMLH1,", "but", "not", "in", "hereditary", "nonpolyposis", "colorectal", "cancer.", "\n\n\n", "##", "PURPOSE" ]
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BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer. ## PURPOSE
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22899730
[ "Among", "1,980", "cases", "tested,", "12%", "were", "BRAF", "c.1799T>A", "(p.V600E)", "mutation-positive", "(n", "=", "247).", "BRAF-mutated", "CRC", "was", "associated", "with", "poorer", "disease-specific", "survival", "adjusting", "for", "age,", "sex,", "time", "from", "diagnosis", "to", "enrollment,", "stage,", "and", "MSI", "status", "(HR,", "1.43;", "95%", "CI,", "1.05-1.95).", "This", "association", "was", "limited", "to", "cases", "diagnosed", "at", "ages", "<50", "(HR,", "3.06;", "95%", "CI,", "1.70-5.52)", "and", "was", "not", "evident", "in", "cases", "with", "MSI-high", "tumors", "(HR,", "0.94;", "95%", "CI,", "0.44-2.03).", "Associations", "with", "overall", "survival", "were", "similar." ]
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Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation-positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70-5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44-2.03). Associations with overall survival were similar.
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26302849
[ "Our", "results", "provide", "evidence", "that", "variants", "of", "PRLHR", "gene", "are", "a", "protective", "factor", "in", "colorectal", "cancer", "and", "variants", "of", "HSPA12A", "gene", "are", "a", "protective", "factor", "in", "gastric", "cancer", "in", "the", "Chinese", "Han", "population." ]
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Our results provide evidence that variants of PRLHR gene are a protective factor in colorectal cancer and variants of HSPA12A gene are a protective factor in gastric cancer in the Chinese Han population.
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12000733
[ "Aberrant", "crypt", "foci", "(ACF)", "are", "postulated", "to", "be", "the", "earliest", "precursor", "lesion", "in", "colorectal", "carcinogenesis,", "and", "CpG", "island", "methylation", "CpG", "island", " ", "methylation", "has", "been", "described", "as", "an", "important", "molecular", "pathway.", "We", "therefore", "studied", "methylation", "in", "ACF", "from", "patients", "with", "familial", "adenomatous", "polyposis", "(FAP)", "or", "sporadic", "colorectal", "cancer.", "We", "assessed", "methylation", "status", "of", "the", "p16", "tumor", "suppressor", "gene,", "MINT1", "(", "methylated", "in", "tumor", "1", "methylation", "methylation", " ", "in", "ACF", "from", "patients", "with", "familial", "adenomatous", "polyposis", "(FAP)", "or", "sporadic", "colorectal", "cancer.", "We", "assessed", "methylation", "status", "of", "the", "p16", " ", "tumor", "suppressor", "gene,", "MINT1", " ", "(methylated", "in", "tumor", "1),", "MINT2", ",", "MINT31,", "O(6)-methylguanine-DNA", "methyltransferase", "gene,", "and", "hMLH1", "mismatch", "repair", "gene.", "We", "compared", "methylation", "to", "ACF", "histopathology,", "K-ras", "proto-oncogene", "mutation,", "loss", "of", "heterozygosity", "at", "chromosome", "1p,", "and", "microsatellite", "instability.", "Methylation", "was", "present", "in", "34%", "(21", "of", "61)", "of", "ACF,", "including", "both", "FAP", "and", "sporadic", "types,", "but", "was", "more", "frequent", "in", "sporadic", "ACF", "[53%", "(18", "of", "34)", "versus", "11%", "(3", "of", "27),", "P", "=", "0.002],", "especially", "dysplastic", "sporadic", "ACF", "[75%", "(3", "of", "4)", "versus", "8%", "(2", "of", "24),", "P", "=", "0.004].", "MINT31", "was", "more", "frequently", "methylated", "in", "heteroplastic", "ACF", "than", "dysplastic", "ACF", "[35%", "(11", "of", "31)", "versus", "7%", "(2", "of", "30),", "P", "=", "0.01].", "Strong", "associations", "of", "ACF", "methylation", "with", "K-ras", "mutation", "(P", "=", "0.007)", "and", "with", "loss", "of", "chromosome", "1p", "(P", "=", "0.04)", "were", "observed,", "but", "methylation", "was", "the", "only", "molecular", "abnormality", "identified", "in", "16%", "(10", "of", "61)", "of", "ACF.", "Our", "findings", "suggest", "that", "methylation", "in", "ACF", "is", "an", "early", "event", "in", "the", "pathogenesis", "of", "a", "subset", "of", "colorectal", "carcinomas,", "and", "that", "ACF", "from", "FAP", "patients", "and", "patients", "with", "sporadic", "colorectal", "cancer", "have", "distinct", "epigenetic", "changes", "that", "reflect", "differences", "in", "molecular", "pathogenesis." ]
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Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesion in colorectal carcinogenesis, and CpG island methylation CpG island methylation has been described as an important molecular pathway. We therefore studied methylation in ACF from patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer. We assessed methylation status of the p16 tumor suppressor gene, MINT1 ( methylated in tumor 1 methylation methylation in ACF from patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer. We assessed methylation status of the p16 tumor suppressor gene, MINT1 (methylated in tumor 1), MINT2 , MINT31, O(6)-methylguanine-DNA methyltransferase gene, and hMLH1 mismatch repair gene. We compared methylation to ACF histopathology, K-ras proto-oncogene mutation, loss of heterozygosity at chromosome 1p, and microsatellite instability. Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation was the only molecular abnormality identified in 16% (10 of 61) of ACF. Our findings suggest that methylation in ACF is an early event in the pathogenesis of a subset of colorectal carcinomas, and that ACF from FAP patients and patients with sporadic colorectal cancer have distinct epigenetic changes that reflect differences in molecular pathogenesis.
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8187091
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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 is involved in the development of moderate adenoma, and loss of heterozygosity of the APC gene is associated with further development to carcinoma. It was also observed that the distribution of 75 somatic mutations from one FAP patient on the APC sequence was similar to the distribution of 159 somatic mutations from 83 patients with FAP and non-FAP, which suggests that the position of somatic mutation 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 mutations , including 3 new hot spots of mutation at codons 1378, 1450, and 1487-1490, which frequently occurred in somatic mutations 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 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 adenomatous polyposis coli gene in colorectal tumors.
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26925673
[ "##", "RESULTS" ]
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## RESULTS
[ 2, 7, 7, 2274, 3 ]
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[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
22810479
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
[ 2, 7, 7, 4355, 3 ]
[ 0, 0, 0, 0, 0 ]
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[ -100, 0, 0, 0, -100 ]
26925673
[ "##", "CONCLUSIONS" ]
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## CONCLUSIONS
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[ -100, 0, 0, 0, -100 ]
25374237
[ "##", "RESULTS" ]
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## RESULTS
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18268114
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Advances in genomics offer new strategies for assessing the association of common genetic variations at multiple loci and risk of many diseases, including colorectal cancer. Low-penetrance alleles of genes in many biological pathways, such as DNA repair, metabolism, inflammation, cell cycle, apoptosis, and Wnt signaling, may influence the risk of nonfamilial colorectal cancer. To identify susceptibility genes for colorectal cancer, we designed a large-scale case-control association study nested within the Nurses' Health Study (190 cases and 190 controls) and the Health Professionals' Follow-up Study (168 cases and 168 controls). We used a custom GoldenGate (Illumina) oligonucleotide pool assay including 1,536 single nucleotide polymorphisms (SNP) selected in candidate genes from cancer-related pathways, which have been sequenced and genotyped in the SNP500Cancer project; 1,412 of the 1,536 (92%) of the SNPs were genotyped successfully within 388 genes. SNPs in high linkage disequilibrium (r(2) >/= 0.90) with another assayed SNP were excluded from further analyses. As expected by chance (and not significant compared with a corrected Bonferroni P = 0.00004), in the additive model, 11 of 1,253 (0.9%) SNPs had a P(trend) < 0.01 and 38 of 1,253 (3.0%) SNPs had a P(trend) >/= 0.01 and P(trend) < 0.05. Of note, the MGMT Lys(178)Arg (rs2308237) SNP, in linkage disequilibrium with the previously reported MGMT Ile(143)Val SNP, had an inverse association with colorectal cancer risk (MGMT Lys(178)Arg: odds ratio, 0.52; 95% confidence interval, 0.35-0.78; unadjusted P(trend) = 0.0003 for the additive model; gene-based test global P = 0.00003). The SNP500Cancer database and the Illumina GoldenGate Assay allowed us to test a larger number of SNPs than previously possible. We identified several SNPs rs2308237 Lys(178)Arg SNP 500Cancer project; 1,412 of the 1,536 (92%) of the SNPs were genotyped successfully within 388 genes. SNPs in high linkage disequilibrium (r(2) >/= 0.90) with another assayed SNP were excluded from further analyses. As expected by chance (and not significant compared with a corrected Bonferroni P = 0.00004), in the additive model, 11 of 1,253 (0.9%) SNPs had a P(trend) < 0.01 and 38 of 1,253 (3.0%) SNPs had a P(trend) >/= 0.01 and P(trend) < 0.05. Of note, the MGMT Lys(178)Arg (rs2308237) SNP variants in candidate genes for colorectal cancer risk in the Nurses' Health Study and the Health Professionals' Follow-up Study.
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19706845
[ "To", "screen", "for", "tagging", "single", "nucleotide", "polymorphisms", "(tag", "SNP", "single", "nucleotide", "polymorphisms", " ", "(tagSNP)", "in", "the", "major", "alcohol", "metabolizing", "enzymes:", "ADH1B,", "ALDH2,", "and", "CYP2E1,", "and", "to", "evaluate", "the", "association", "between", "these", "tagSNPs", "and", "colorectal", "cancer", "(CRC)", "in", "a", "southwestern", "Chinese", "population." ]
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To screen for tagging single nucleotide polymorphisms (tag SNP single nucleotide polymorphisms (tagSNP) in the major alcohol metabolizing enzymes: ADH1B, ALDH2, and CYP2E1, and to evaluate the association between these tagSNPs and colorectal cancer (CRC) in a southwestern Chinese population.
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14734469
[ "##", "CONCLUSIONS" ]
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## CONCLUSIONS
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22895193
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Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations fusions in colon cancer.
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22899730
[ "##", "RESULTS" ]
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## RESULTS
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22899730
[ "##", "IMPACT" ]
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## IMPACT
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19706845
[ "##", "CONCLUSION" ]
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## CONCLUSION
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26302849
[ "Our", "results", "provide", "evidence", "that", "variants", " ", "of", "PRLHR", "gene", "are", "a", "protective", "factor", "in", "colorectal", "cancer", "and", "variants", "C11orf93-C11orf92", " ", "genes", "are", "associated", "with", "the", "risk", "of", "gastric", "and", "colorectal", "cancers", "in", "the", "Chinese", "Han", "population." ]
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Our results provide evidence that variants of PRLHR gene are a protective factor in colorectal cancer and variants C11orf93-C11orf92 genes are associated with the risk of gastric and colorectal cancers in the Chinese Han population.
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23497483
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Our findings provide evidence of the utility of RNA-Seq in mutation variants Mutation spectrum in human colorectal cancers and potential functional relevance. ## BACKGROUND
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24196785
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We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1 , which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.
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18550572
[]
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26446363
[ "The", "majority", "of", "pathogenic", "mismatch", "repair", "(MMR)", "gene", "mutations", "detected", "in", "Lynch", "syndrome", "patients", "are", "truncating", "(frameshift", "or", "nonsense).", "However,", "the", "classification", "of", "terminal", "truncating", "mutations", "is", "sometimes", "difficult", "and", "predictive", "testing", "based", "on", "non-deleterious", "variants", "truncating", "mutations", " ", "are", "equal." ]
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The majority of pathogenic mismatch repair (MMR) gene mutations detected in Lynch syndrome patients are truncating (frameshift or nonsense). However, the classification of terminal truncating mutations is sometimes difficult and predictive testing based on non-deleterious variants truncating mutations are equal.
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26416897
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
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24568449
[ "##", "METHODOLOGY/PRINCIPAL", "FINDINGS" ]
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## METHODOLOGY/PRINCIPAL FINDINGS
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17938238
[ "The", "genetic", "basis", "of", "sporadic", "colorectal", "cancer", "has", "illuminated", "our", "knowledge", "of", "human", "cancer", "genetics.", "This", "has", "been", "facilitated", "and", "catalyzed", "by", "an", "appreciation", "and", "deep", "understanding", "of", "the", "forms", "of", "colorectal", "cancer", "that", "harbor", "an", "inherited", "predisposition,", "including", "familial", "adenomatous", "polyposis", "(FAP),", "hereditary", "nonpolyposis", "colorectal", "cancer", "(HNPCC)", "or", "Lynch", "syndrome,", "the", "hamartomatous", "polyposis", "syndromes,", "and", "certain", "other", "rare", "syndromes.", "Identification", "of", "germline", "mutations", " ", "in", "pivotal", "genes", "underlying", "the", "inherited", "forms", "of", "colorectal", "cancer", "has", "yielded", "many", "dividends,", "including", "functional", "dissection", "of", "critical", "molecular", "pathways", "that", "have", "been", "revealed", "to", "be", "important", "in", "development,", "cellular", "homeostasis,", "and", "cancer;", "new", "approaches", "in", "chemoprevention,", "molecular", "diagnostics", "and", "genetic", "testing,", "and", "therapy;", "and", "underscoring", "genotypic-phenotypic", "relationships." ]
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The genetic basis of sporadic colorectal cancer has illuminated our knowledge of human cancer genetics. This has been facilitated and catalyzed by an appreciation and deep understanding of the forms of colorectal cancer that harbor an inherited predisposition, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, the hamartomatous polyposis syndromes, and certain other rare syndromes. Identification of germline mutations in pivotal genes underlying the inherited forms of colorectal cancer has yielded many dividends, including functional dissection of critical molecular pathways that have been revealed to be important in development, cellular homeostasis, and cancer; new approaches in chemoprevention, molecular diagnostics and genetic testing, and therapy; and underscoring genotypic-phenotypic relationships.
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9841584
[]
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20646601
[ "To", "determine", "the", "mutation", "status", "of", "K-ras", " ", "gene", "in", "colorectal", "cancer", "and", "analyze", "the", "associations", "between", "its", "mutation", "status", "and", "clinicopathological", "characteristics", "in", "colorectal", "cancer", "so", "as", "to", "select", "the", "patients", "likely", "to", "benefit", "from", "a", "targeted", "therapy." ]
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To determine the mutation status of K-ras gene in colorectal cancer and analyze the associations between its mutation status and clinicopathological characteristics in colorectal cancer so as to select the patients likely to benefit from a targeted therapy.
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22899730
[ "##", "IMPACT" ]
[ 0, 0 ]
## IMPACT
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9609758
[ "##", "CONCLUSIONS" ]
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## CONCLUSIONS
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20459617
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
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26302849
[ "The", "genotype", "\"A/T\"", "of", "rs12413624", "in", "PRLHR", "gene", "was", "associated", "with", "a", "decreased", "risk", "of", "colorectal", "cancer", "in", "allele", "model", "analysis", "[odds", "ratio", "(OR)", " ", "=", " ", "0.81;", "95%", "confidence", "interval", "(CI)", " ", "=", " ", "0.68-0.97;", "p", " ", "=", " ", "0.018]", "and", "log-additive", "model", "analysis", "(OR", " ", "=", " ", "0.81;", "95%", "CI", " ", "=", " ", "0.66-0.98;", "p", " ", "=", " ", "0.032).", "The", "genotype", "\"A/G\"", "of", "rs1665650", "in", "HSPA12A", "gene", "was", "associated", "with", "a", "decreased", "risk", "of", "gastric", "cancer", "in", "overdominant", "model", "analysis", "(OR", " ", "=", " ", "0.77;", "95%", "CI", " ", "=", " ", "0.60-0.99;", "p", " ", "=", " ", "0.038)." ]
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The genotype "A/T" of rs12413624 in PRLHR gene was associated with a decreased risk of colorectal cancer in allele model analysis [odds ratio (OR)   =   0.81; 95% confidence interval (CI)   =   0.68-0.97; p   =   0.018] and log-additive model analysis (OR   =   0.81; 95% CI   =   0.66-0.98; p   =   0.032). The genotype "A/G" of rs1665650 in HSPA12A gene was associated with a decreased risk of gastric cancer in overdominant model analysis (OR   =   0.77; 95% CI   =   0.60-0.99; p   =   0.038).
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16924054
[ "We", "report", "the", "case", "of", "a", "54-year-old", "man", "with", "a", "2-year", "history", "of", "skin-colored", "papules", "clinically", "reminiscent", "of", "large", "sebaceous", "hyperplasias", "on", "the", "nose", "and", "back,", "but", "histologically", "diagnosed", "as", "sebaceous", "adenomas", "and", "epitheliomas.", "His", "family", "history", "was", "positive", "for", "colon", "cancer", "in", "the", "mother", "and", "2", "brothers.", "A", "colonoscopy", "done", "during", "the", "hospitalization", "revealed", "2", "sessile", "polyps", "in", "the", "left", "colon,", "both", "showing", "a", "low-grade", "dysplasia", "on", "the", "biopsy", "specimen.", "Immunohistochemical", "staining", "performed", "on", "the", "cutaneous", "and", "colic", "biopsy", "specimens", "revealed", "a", "lack", "of", "expression", "of", "MSH-2", " ", "and", "MSH-6", ".", "Genetic", "testing", "revealed", "microsatellite", "instability", "in", "the", "colon", "and", "cutaneous", "tumors." ]
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We report the case of a 54-year-old man with a 2-year history of skin-colored papules clinically reminiscent of large sebaceous hyperplasias on the nose and back, but histologically diagnosed as sebaceous adenomas and epitheliomas. His family history was positive for colon cancer in the mother and 2 brothers. A colonoscopy done during the hospitalization revealed 2 sessile polyps in the left colon, both showing a low-grade dysplasia on the biopsy specimen. Immunohistochemical staining performed on the cutaneous and colic biopsy specimens revealed a lack of expression of MSH-2 and MSH-6 . Genetic testing revealed microsatellite instability in the colon and cutaneous tumors.
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24568449
[ "MicroRNAs", "(miRNAs)", "are", "an", "abundant", "class", "of", "endogenous", "small", "non-coding", "RNAs", "of", "20-25", "nucleotides", "in", "length", "that", "function", "as", "negative", "gene", "regulators.", "MiRNAs", "play", "roles", "in", "most", "biological", "processes,", "as", "well", "as", "diverse", "human", "diseases", "including", "cancer.", "Recently,", "many", "studies", "investigated", "the", "association", "between", "SNPs", "in", "miR-146a", "SNPs", " ", "in", "miR-146a", "rs2910164,", "miR-196a2", "rs11614913,", "miR-149", "miR-196a2", " ", "rs11614913,", "miR-149", "rs229283,", "miR-499", " ", "rs3746444", "and", "colorectal", "cancer", "(CRC),", "which", "results", "have", "been", "inconclusive." ]
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MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive.
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12534642
[ "(i)", "CYP1A2", "polymorphisms", " ", "are", "in", "linkage", "disequilibrium.", "Therefore,", "only", "-164A-->C", "(CYP1A2*1F)", "and", "-2464T-->delT", "-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." ]
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(i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only -164A-->C (CYP1A2*1F) and -2464T-->delT -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.
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22810479
[ "##", "MAIN", "OUTCOME", "MEASURES" ]
[ 0, 0, 0, 0 ]
## MAIN OUTCOME MEASURES
[ 2, 7, 7, 2730, 3924, 3975, 3 ]
[ 0, 0, 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, -100 ]
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", "SNP", "SNPs", "ALDH2", ",", "and", "CYP2E1,", "and", "to", "evaluate", "the", "association", "between", "these", "tagSNPs", "and", "colorectal", "cancer", "(CRC)", "in", "a", "southwestern", "Chinese", "population." ]
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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 SNP SNPs ALDH2 , and CYP2E1, and to evaluate the association between these tagSNPs and colorectal cancer (CRC) in a southwestern Chinese population.
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24196785
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
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", "polyposis", "mutation", " ", "in", "the", "polyposis", "gene,", "DNA", "analysis", "might", "be", "helpful", "in", "treatment", "decisions." ]
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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 polyposis mutation in the polyposis gene, DNA analysis might be helpful in treatment decisions.
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9439149
[ "Microsatellites", "are", "short", "repeated", "oligonucleotide", "sequences", "found", "throughout", "the", "human", "genome.", "High", "mutation", "rates", "in", "microsatellite", "sequences", "have", "been", "found", "in", "tumors", "from", "patients", "with", "hereditary", "non-polyposis", "colorectal", "carcinoma", "and", "some", "sporadic", "carcinomas.", "However,", "little", "information", "is", "available", "regarding", "RER-positive", "phenotype", "in", "gastric", "carcinomas,", "particularly", "in", "terms", "of", "age", "of", "onset", "and", "other", "pathologic", "features,", "such", "as", "histologic", "types,", "degree", "of", "differentiation,", "location", "or", "stage", "of", "the", "carcinoma." ]
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Microsatellites are short repeated oligonucleotide sequences found throughout the human genome. High mutation rates in microsatellite sequences have been found in tumors from patients with hereditary non-polyposis colorectal carcinoma and some sporadic carcinomas. However, little information is available regarding RER-positive phenotype in gastric carcinomas, particularly in terms of age of onset and other pathologic features, such as histologic types, degree of differentiation, location or stage of the carcinoma.
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9841584
[ "##", "PATIENTS" ]
[ 0, 0 ]
## PATIENTS
[ 2, 7, 7, 2132, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
12534642
[ "(i)", "CYP1A2", "polymorphisms", "are", "in", "linkage", "disequilibrium.", "Therefore,", "only", "-164A-->C", "(", "CYP1A2*1F", "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." ]
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(i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only -164A-->C ( CYP1A2*1F 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.
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20661832
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We show, for the first time, that hydrophobic bile acids cause aberrations of the mitotic machinery of colon cells that can give rise to aneuploidy, the chromosomal perturbations common in colon tumors. First, we show that DOC induces a statistically significant fourfold increase in the number of micronuclei in NCM-460 cells (a noncancerous colon cell line) and a threefold increase in the number of micronuclei in binucleated HT-29 colon cancer cells using the cytokinesis block micronucleus assay. Second, we observed mitotic aberrations after DOC treatment, including improper alignment of chromosomes at the metaphase plate, lagging chromosomes during anaphase, anaphase/telophase chromatin bridges, multipolar divisions, and formation of polynucleated cells. It was determined that there was a statistically significant threefold increase in the number of aberrant metaphases after short-term and long-term exposure of HT-29 and HCT-116 cells, respectively. Third, we showed with Western blots and immunohistochemistry that a likely basis for these mitosis-related perturbations included decreased expression of the spindle checkpoint proteins, Mad2, BubR1, and securin Mad2 , BubR1 , and securin. Fourth, results of DOC treatment on nocodazole-challenged cells further indicated deficiencies in activation of the spindle assembly checkpoint. This study provides mechanisms by which hydrophobic bile acids can induce genomic instability in colon epithelial cells.
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23132392
[]
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26416897
[ "##", "RESULTS" ]
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## RESULTS
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14734469
[ "##", "EXPERIMENTAL", "DESIGN" ]
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## EXPERIMENTAL DESIGN
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