A gene-environment-induced epigenetic program initiates tumorigenesis.

ABSTRACT: Tissue damage increases the risk of cancer through poorly understood mechanisms¹. In mouse models of pancreatic cancer, pancreatitis associated with tissue injury collaborates with activating mutations in the Kras oncogene to markedly accelerate the formation of early neoplastic lesions and, ultimately, adenocarcinoma^2,3. Here, by integrating genomics, single-cell chromatin assays and spatiotemporally controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48

SUBMITTER: Alonso-Curbelo D 

PROVIDER: S-EPMC8482641 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature