DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and CTCs.

ABSTRACT: Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16-related interfer

SUBMITTER: Guo H 

PROVIDER: S-EPMC10436379 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature