TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states.

ABSTRACT: Mutations in cancer risk genes increase susceptibility, but not all carriers develop cancer. Indeed, while DNA mutations are necessary drivers of cancer, only a small subset of mutated cells go on to cause the disease. To date, the mechanisms underlying individual cancer susceptibility remain unclear. Here, we took advantage of a unique mouse model of intrinsic developmental heterogeneity (Trim28^+/D9) to investigate whether early-life epigenetic variation influences cancer susceptibility later in life. We found that heterozygosity of Trim28 is sufficient to generate two distinct early-life epigenetic states associated with differing cancer susceptibility. These developmentally primed states exhibit differential methylation patterns at typically silenced heterochromatin, detectab

SUBMITTER: Panzeri I 

PROVIDER: S-EPMC11864977 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature