Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy.

ABSTRACT: The global impact of somatic structural variants (SVs) on gene regulation in advanced tumors with complex treatment histories has been mostly uncharacterized. Here, using whole-genome and RNA sequencing from 570 recurrent or metastatic tumors, we report the altered expression of hundreds of genes in association with nearby SV breakpoints, including oncogenes and G-protein-coupled receptor-related genes such as PLEKHG2. A significant fraction of genes with SV-expression associations correlate with worse patient survival in primary and advanced cancers, including SRD5A1. In many instances, SV-expression associations involve retrotransposons being translocated near genes. High overall SV burden is associated with treatment with DNA alkylating agents or taxanes and altered expression of metabo

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8630779 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature