Pan-cancer inference of intra-tumor heterogeneity reveals associations with different forms of genomic instability.

ABSTRACT: Genomic instability is a major driver of intra-tumor heterogeneity. However, unstable genomes often exhibit different molecular and clinical phenotypes, which are associated with distinct mutational processes. Here, we algorithmically inferred the clonal phylogenies of ~6,000 human tumors from 32 tumor types to explore how intra-tumor heterogeneity depends on different implementations of genomic instability. We found that extremely unstable tumors associated with DNA repair deficiencies or high chromosomal instability are not the most intrinsically heterogeneous. Conversely, intra-tumor heterogeneity is greatest in tumors exhibiting relatively high numbers of both mutations and copy number alterations, a feature often observed in cancers associated with exogenous mutagens. Independently of

SUBMITTER: Raynaud F 

PROVIDER: S-EPMC6155543 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature