MYC ecDNA promotes intratumour heterogeneity and plasticity in PDAC.

ABSTRACT: Intratumour heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance^1,2. Oncogene dosage variation contributes to cell-state transitions and phenotypic heterogeneity³, thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood. Here we show that extrachromosomal DNA (ecDNA) is a major source of high-level focal amplification in key oncogenes and a major contributor of MYC heterogeneity in pancreatic ductal adenocarcinoma (PDAC). We demonstrate that ecDNAs drive varying levels of MYC dosage, depending on their regulatory landscape, enabling cancer cells to rapidly and reversibly adapt to microenvironmental changes. In the absence of selective pre

SUBMITTER: Fiorini E 

PROVIDER: S-EPMC12003172 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature