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CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer
Author(s) -
KIM HEE CHEOL,
ROH SUN AE,
GA IN HWA,
KIM JUNGSUN,
YU CHANG SIK,
KIM JIN CHEON
Publication year - 2005
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2005.03943.x
Subject(s) - methylation , microsatellite instability , dna methylation , cpg site , colorectal cancer , carcinogenesis , adenoma , cancer research , cancer , medicine , biology , oncology , pathology , gene , microsatellite , genetics , gene expression , allele
Background and Aims: CpG island methylation is present in various tumors, including colorectal carcinomas, and is thought to be an important mechanism in carcinogenesis. We evaluated the methylation status of primary colorectal tumors to determine its role in the adenoma to carcinoma sequence. Methods: The methylation status of APC, THBS1, MGMT, hMLH1 and GSTP1 , as determined by methylation specific PCR (MSP), and microsatellite instability (MSI) using three mononucleotide markers were assessed in 40 colorectal adenomas and 36 adenocarcinomas. The correlations of methylation status and MSI with the clinicopathologic parameters of the tumors were determined. Results: Of the 40 adenomas, 24 (60%) were methylated at one or more loci, and 12 (30%) at two or more loci (CpG island methylation phenotype‐high, CIMP‐H). Of 36 carcinomas, 27 (75%) were methylated at one or more loci and 11 (30.5%) at two or more loci (CIMP‐H). THBSI was the most frequently methylated locus in both adenomas ( n = 19, 47.5%) and carcinomas ( n = 16, 44.4%). Overall, methylation status of adenomas and carcinomas did not differ significantly ( P = 0.53), nor did the methylation status of individual genes. For adenomas, size ( P = 0.049) and histologic classification of the villous components ( P = 0.018) were each associated with methylation status. For carcinomas, however, no clinicopathologic variable was related to methylation status. MSI was detected in three adenomas (7.5%) and five carcinomas (13.9%), and was closely correlated with hMLH1 methylation ( P < 0.001). Conclusions: In colorectal tumors, CpG island methylation of tumor suppressor genes appears to be common and may be involved in the progression of adenomas. © 2005 Blackwell Publishing Asia Pty Ltd