Genetic similarity between cancers and comorbid Mendelian diseases identifies candidate driver genes
Despite large-scale cancer genomics studies, key somatic mutations driving cancer, and their functional roles, remain elusive. Here, we propose that analysis of comorbidities of Mendelian diseases with cancers provides a novel, systematic way to discover new cancer genes. If germline genetic variation in Mendelian loci predisposes bearers to common cancers, the same loci may harbour cancer-associated somatic variation. Compilations of clinical records spanning over 100 million patients provide an unprecedented opportunity to assess clinical associations between Mendelian diseases and cancers. We systematically compare these comorbidities against recurrent somatic mutations from more than 5,000 patients across many cancers. Using multiple measures of genetic similarity, we show that a Mendelian disease and comorbid cancer indeed have genetic alterations of significant functional similarity. This result provides a basis to identify candidate drivers in cancers including melanoma and glioblastoma. Some Mendelian diseases demonstrate 'pan-cancer' comorbidity and shared genetics across cancers.
- Profiling Reactive Metabolites via Chemical Trapping and Targeted Mass Spectrometry
- Does the brain listen to the gut?
- (Meta)genomic insights into the pathogenome of Cellulosimicrobium cellulans
- A robust adaptive denoising framework for real-time artifact removal in scalp EEG measurements
- Imputing Gene Expression in Uncollected Tissues Within and Beyond GTEx
- Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break
- Controlling the Cyanobacterial Clock by Synthetically Rewiring Metabolism
- Choosing experiments to accelerate collective discovery
- The transcriptional landscape of age in human peripheral blood
- Digital signaling decouples activation probability and population heterogeneity