Oxidative DNA damage induces hypomethylation in a compromised base excision repair colorectal tumourigenesis.

ABSTRACT:

Background

A compromised base excision repair (BER) promotes carcinogenesis by accumulating oxidative DNA-damaged products as observed in MUTYH-associated polyposis, a hereditary colorectal cancer syndrome marked by adenomas and cancers with an accumulation of 8-oxoguanine. Remarkably, DNA global demethylation has been shown to be mediated by BER, suggesting a relevant interplay with early colorectal tumourigenesis. To check this hypothesis, we investigated a cohort of 49 adenomas and 10 carcinomas, derived from 17 MUTYH-associated polyposis patients; as adenoma controls, we used a set of 36 familial adenomatous polyposis and 24 sporadic polyps.

Methods

Samples were analysed for their mutational and epigenetic status, measured as global LINE-1 (long interspersed nuclear elem

SUBMITTER: Furlan D 

PROVIDER: S-EPMC5355935 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature