Pan-Cancer Comparative and Integrative Analyses of Driver Alterations Using Japanese and International Genomic Databases
AbstractUsing 48,627 samples from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), we present a pan-cancer landscape of driver alterations and their clinical actionability in Japanese patients. Comparison with White patients in Genomics Evidence Neoplasia Information Exchange (GENIE) demonstrates high TP53 mutation frequencies in Asian patients across multiple cancer types. Integration of C-CAT, GENIE, and The Cancer Genome Atlas data reveals many cooccurring and mutually exclusive relationships between driver mutations. At pathway level, mutations in epigenetic regulators frequently cooccur with PI3K pathway molecules. Furthermore, we found significant cooccurring mutations within the epigenetic pathway. Accumulation of mutations in epigenetic regulators causes increased proliferation-related transcriptomic signatures. Loss-of-function of many epigenetic drivers inhibits cell proliferation in their wild-type cell lines, but this effect is attenuated in those harboring