Mutations in DNA repair genes are known drivers of hereditary cancers. However, only a small fraction of patients with hereditary breast or ovarian cancers has BRCA1/2 mutations, which are involved in homologous recombination (HR) DNA repair.
Researchers led by Nidhi Sahni, Ph.D., calculated scores across tumors from The Cancer Genome Atlas to comprehensively identify tumors that were either positive or negative for HR defects. Around 75% of tumors with a positive HR score did not have defects in known HR genes, but the researchers identified nearly 100 candidate HR-related genes. They found that RNA-binding protein (RBP) genes were particularly enriched in genome-wide screens for cancer risk, highlighting their potential role as drivers of HR repair.
Previous studies have linked RBPs to DNA damage repair, and this study provides further insights into specific RBPs and their role as novel drivers of HR deficiency, either directly or via regulating other HR repair genes. These findings have implications for screening, patient risk stratification and developing therapeutic strategies.