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

Autor: Yiqun Zhang, Fengju Chen, Erin Pleasance, Laura Williamson, Cameron J. Grisdale, Emma Titmuss, Janessa Laskin, Steven J.M. Jones, Isidro Cortes-Ciriano, Marco A. Marra, Chad J. Creighton
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Reports, Vol 37, Iss 7, Pp 110023- (2021)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.110023
Popis: Summary: 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 metabolism-associated genes. SV-expression associations within tumors from topoisomerase I inhibitor-treated patients include chromatin-related genes. Within anthracycline-treated tumors, SV breakpoints near chromosome 1p genes include PDE4B. Patient treatment and history can help understand the widespread SV-mediated cis-regulatory alterations found in cancer.
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