DNA hypermethylation appears early and shows increased frequency with dysplasia in Lynch syndrome-associated colorectal adenomas and carcinomas.

ABSTRACT:

Background

Lynch syndrome (LS) is associated with germline mutations in DNA mismatch repair (MMR) genes. The first "hit" to inactivate one allele of the predisposing MMR gene is present in every cell, contributing to accelerated tumorigenesis. Less information is available of the nature, timing, and order of other molecular "hits" required for tumor development. To this end, MMR protein expression and coordinated promoter methylation were examined in colorectal specimens prospectively collected from LS mutation carriers (n = 55) during colonoscopy surveillance (10/2011-5/2013), supplemented with retrospective specimens.

Results

Loss of MMR protein corresponding to the gene mutated in the germline increased with dysplasia, with frequency of 0 % in normal mucosa, 50-68 % in lo

SUBMITTER: Valo S 

PROVIDER: S-EPMC4511034 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature