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dc.contributor.author
Reyna, Matthew A.
dc.contributor.author
Haan, David
dc.contributor.author
Paczkowska, Marta
dc.contributor.author
Verbeke, Lieven P.C.
dc.contributor.author
Vazquez, Miguel
dc.contributor.author
Kahraman, Abdullah
dc.contributor.author
Pulido-Tamayo, Sergio
dc.contributor.author
Barenboim, Jonathan
dc.contributor.author
Wadi, Lina
dc.contributor.author
Dhingra, Priyanka
dc.contributor.author
Shrestha, Raunak
dc.contributor.author
Getz, Gad
dc.contributor.author
Lawrence, Michael S.
dc.contributor.author
Pedersen, Jakob S.
dc.contributor.author
Rubin, Mark A.
dc.contributor.author
Wheeler, David A.
dc.contributor.author
Brunak, Søren
dc.contributor.author
Izarzugaza, Jose M.G.
dc.contributor.author
Khurana, Ekta
dc.contributor.author
Marchal, Kathleen
dc.contributor.author
Von Mering, Christian
dc.contributor.author
Sahinalp, S. Cenk
dc.contributor.author
Valencia, Alfonso
dc.contributor.author
PCAWG Drivers
dc.contributor.author
Raphael, Benjamin J.
dc.contributor.author
PCAWG Consortium
dc.date.accessioned
2020-02-14T08:01:26Z
dc.date.available
2020-02-14T03:23:18Z
dc.date.available
2020-02-14T08:01:26Z
dc.date.issued
2020
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-020-14367-0
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/399365
dc.identifier.doi
10.3929/ethz-b-000399365
dc.description.abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Pathway and network analysis of more than 2500 whole cancer genomes
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-02-05
ethz.journal.title
Nature Communications
ethz.journal.volume
11
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
729
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2020-02-14T03:23:40Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-02-14T08:01:37Z
ethz.rosetta.lastUpdated
2020-02-14T08:01:38Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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