Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.

ABSTRACT:

Background

Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations. We aimed to characterise genetic and gene regulatory changes associated with primary CME to elucidate possible underlying molecular mechanisms.

Methods

Four carriers of a primary CME and three non-methylated relatives carrying the same genetic haplotype were included. Genetic alterations were sought u

SUBMITTER: Climent-Canto P 

PROVIDER: S-EPMC11686911 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature