Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes

Abstract Mutational processes in tumors create distinctive patterns of mutations, composed of neutral “passenger” mutations and oncogenic drivers that have quantifiable effects on the proliferation and survival of cancer cell lineages. Increases in proliferation and survival are mediated by natural selection, which can be quantified by comparing the frequency at which we detect substitutions to the frequency at which we expect to detect substitutions assuming neutrality. Most of the variants detectable with whole-exome sequencing in tumors are neutral or nearly