PBRM1 Inactivation Promotes Upregulation of Human Endogenous Retroviruses in a HIF-Dependent Manner.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is considered an immunotherapy-responsive disease; however, the reasons for this remain unclear. Studies have variably implicated PBRM1 mutations as a predictive biomarker of immune checkpoint blockade (ICB) response, and separate studies demonstrate that expression of human endogenous retroviruses (hERV) might be an important class of tumor-associated antigens. We sought to understand whether specific mutations were associated with hERV expression. Two large, annotated genomic datasets, TCGA KIRC and IMmotion150, were used to correlate mutations and hERV expression. PBRM1 mutations were consistently associated with increased hERV expression in primary tumors. In vitro silencing of PBRM1, HIF1A, and HIF2A followed by RNA sequencing was performed in U

SUBMITTER: Zhou M 

PROVIDER: S-EPMC8898299 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature