Increased genomic instability and reshaping of tissue microenvironment underlie oncogenic properties of Arid1a mutations.

ABSTRACT: Oncogenic mutations accumulating in many chromatin-associated proteins have been identified in different tumor types. With a mutation rate from 10 to 57%, ARID1A has been widely considered a tumor suppressor gene. However, whether this role is mainly due to its transcriptional-related activities or its ability to preserve genome integrity is still a matter of intense debate. Here, we show that ARID1A is largely dispensable for preserving enhancer-dependent transcriptional regulation, being ARID1B sufficient and required to compensate for ARID1A loss. We provide in vivo evidence that ARID1A is mainly required to preserve genomic integrity in adult tissues. ARID1A loss primarily results in DNA damage accumulation, interferon type I response activation, and chronic inflammation leading

SUBMITTER: D'Ambrosio A 

PROVIDER: S-EPMC10942108 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature