A subset of hyperplastic polyps and sessile serrated polyps show mutations in the BRAF gene and abnormal DNA methylation, which can, ultimately, affect the promoter regions of key DNA-repair and tumor suppressor genes, such as MLH1 and MGMT, leading to their decreased transcription and microsatellite instability.
Mixed polyps, particularly those with carcinoma, showed loss of hMLH1 (33%), MGMT (37%), and even hMSH2 (11%) with significantly higher frequency compared to hyperplastic polyps, conventional adenomas, and serrated adenomas.
Consequently, we have assessed in colon adenomas and hyperplastic polyps the methylation status of MGMT, CDKN2A, and MLH1 to determine the timing and frequency of these events in the polyp-carcinoma progression sequence and subsequently to analyze the potential for these methylated genes to be molecular markers for adenomas and hyperplastic polyps.