DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways.

ABSTRACT:

Background

Aberrations in DNA methylation are widespread in colon cancer (CC). Understanding origin and progression of DNA methylation aberrations is essential to develop effective preventive and therapeutic strategies. Here, we aimed to dissect CC subtype-specific methylation instability to understand underlying mechanisms and functions.

Methods

We have assessed genome-wide DNA methylation in the healthy normal colon mucosa (HNM), precursor lesions and CCs in a first comprehensive study to delineate epigenetic change along the process of colon carcinogenesis. Mechanistically, we used stable cell lines, genetically engineered mouse model of mutant BRAF^V600E and molecular biology analysis to establish the role of BRAF^V600E-mediated-TET inhibition in CpG-

SUBMITTER: Noreen F 

PROVIDER: S-EPMC6916434 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature