Meta-analysis reveals differences in somatic alterations by genetic ancestry across common cancers

Genetic similarity of populations (or genetic ancestry) is associated with differences in somatic alterations in cancers. We meta-analyze two targeted panel sequencing cohorts with 275,605 samples from 14 cancer types. Here we find a recurrent depletion of TERT promoter mutations in patients of African and East Asian ancestry across multiple cancers. Several clinically actionable alterations, such as ERBB2 mutations in lung adenocarcinoma and MET mutations in papillary renal cell carcinoma, occur at a higher frequency in patients of non-European ancestry. Furthermore, in both cohorts, we show depletions in total driver alterations in non-European ancestries in multiple cancer types, potentially reflecting biases in current panel-based testing that prioritize established targets derived from predominantly patients of European ancestry. Our study highlights a need to increase population diversity in genomic studies to find new drivers and enhance precision oncology interventions for all populations.