The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer.

ABSTRACT: Large-scale human genetic data^1-3 have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)^4-6. VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2α (HIF2A) stabilization^6,7. We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers

SUBMITTER: Patel SA 

PROVIDER: S-EPMC9242860 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature