Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

ABSTRACT: Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take

SUBMITTER: Ma P 

PROVIDER: S-EPMC5634994 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature