Ancestry Influences on the Molecular Presentation of Tumours

Abstract

Epidemiological studies have identified innumerable ways in which cancer presentation and behaviour is associated with patient ancestry. The molecular bases for these relationships remain largely unknown. We analyzed ancestry associations in the somatic mutational landscape of 12,774 tumours across 33 tumour-types, including 2,562 with whole-genome sequencing. Ancestry influences both the number of mutations in a tumour and the evolutionary timing of when they occur. Specific mutational signatures are associated with ancestry, reflecting potential differences in exogenous and endogenous oncogenic processes. A subset of known cancer driver genes was mutated in ancestry-associated patterns, with transcriptomic consequences. Cancer genome sequencing data is not well-balanced in epidemiologic factors; these data suggest ancestry strongly shapes the somatic mutational landscape of cancer, with potential functional implications.