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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	cancer structural variation structural variants genomic rearrangement whole genome sequencing pan-cancer Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/edab694d74344c2b892a199e86fb5c24
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spelling	oai:doaj.org-article:edab694d74344c2b892a199e86fb5c242021-11-18T04:48:00ZRearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy2211-124710.1016/j.celrep.2021.110023https://doaj.org/article/edab694d74344c2b892a199e86fb5c242021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721015059https://doaj.org/toc/2211-1247Summary: 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.Yiqun ZhangFengju ChenErin PleasanceLaura WilliamsonCameron J. GrisdaleEmma TitmussJanessa LaskinSteven J.M. JonesIsidro Cortes-CirianoMarco A. MarraChad J. CreightonElsevierarticlecancerstructural variationstructural variantsgenomic rearrangementwhole genome sequencingpan-cancerBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 110023- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer structural variation structural variants genomic rearrangement whole genome sequencing pan-cancer Biology (General) QH301-705.5
spellingShingle	cancer structural variation structural variants genomic rearrangement whole genome sequencing pan-cancer Biology (General) QH301-705.5 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 Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
description	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.
format	article
author	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
author_facet	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
author_sort	Yiqun Zhang
title	Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
title_short	Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
title_full	Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
title_fullStr	Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
title_full_unstemmed	Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
title_sort	rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/edab694d74344c2b892a199e86fb5c24
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Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy

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