Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy.
Cell Rep
; 37(7): 110023, 2021 11 16.
Article
em En
| MEDLINE
| ID: mdl-34788622
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 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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Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Variação Estrutural do Genoma
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Recidiva Local de Neoplasia
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article