Genetic and Epigenetic Reprogramming of Transposable Elements Drives ecDNA-Mediated Metastatic Prostate Cancer.

ABSTRACT: Extrachromosomal DNAs (ecDNAs), which replicate and segregate in a non-Mendelian manner, serve as vectors for accelerated tumor evolution. By integrating chromatin accessibility, whole-genome sequencing, and Hi-C-based genome topology data from a cohort of metastatic Castration-Resistant Prostate Cancer (mCRPC) cases, we show that epigenetically activated repeat DNA, amplified in ecDNAs, drive oncogene overexpression. Specifically, we identify a subgroup of mCRPCs (20%) characterized by clusters of accessible LINE1 repeat DNA elements flanking the androgen receptor (AR) gene. These LINE1 elements are co-amplified with AR and provide binding sites for prostate-lineage transcription factors, including AR, FOXA1 and HOXB13. Accessible LINE1 elements establish novel 3D chromatin interactions w

SUBMITTER: Mout L 

PROVIDER: S-EPMC12363880 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature