BRAF^V600E maintains the CpG island methylator phenotype, and DNA methylation of PRC2 targets genes in colon cancer.

ABSTRACT: In colon cancer, the BRAF^V600E mutation is strongly associated with the CpG island methylator phenotype (CIMP). Here, we characterized the contribution of BRAF^V600E to maintenance of aberrant DNA methylation using CRISPR-LbCpf1-corrected BRAF (V600E) organoids. DNA methylation analyses identified 5,187 differentially methylated CpGs within CpG islands-82% hypermethylated in BRAF^V600E organoids-including CIMP-associated genes and polycomb repressor complex 2 (PRC2) target genes. RNA sequencing showed concordant repression of these genes. Furthermore, BRAF^V600E organoids demonstrated high expression of PRC2 core components (EZH2, SUZ12, and EED), showed PRC2-induced H3K27 trimethylation in promoter regions, and maintained a PRC2-associated e

SUBMITTER: El Bouazzaoui L 

PROVIDER: S-EPMC12269043 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature