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Pathway and network...
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Reyna, Matthew APrinceton University
(författare)
Pathway and network analysis of more than 2500 whole cancer genomes
- Artikel/kapitelEngelska2020
Förlag, utgivningsår, omfång ...
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2020-02-05
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Springer Science and Business Media LLC,2020
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17 s.
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:610d765e-e812-47d6-9ff4-11c54db0a343
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https://lup.lub.lu.se/record/610d765e-e812-47d6-9ff4-11c54db0a343URI
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https://doi.org/10.1038/s41467-020-14367-0DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-431723URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:143012858URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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CW medlem i PCAWG Consortium.
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Haan, DavidUniversity of California, Santa Cruz
(författare)
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Paczkowska, MartaOntario Institute for Cancer Research
(författare)
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Verbeke, Lieven P CGhent University
(författare)
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Vazquez, MiguelCentro Nacional de Supercomputación
(författare)
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Kahraman, AbdullahUniversity of Zurich
(författare)
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Pulido-Tamayo, SergioGhent University
(författare)
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Barenboim, JonathanOntario Institute for Cancer Research
(författare)
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Wadi, LinaOntario Institute for Cancer Research
(författare)
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Dhingra, PriyankaWeill Cornell Medicine
(författare)
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Shrestha, RaunakVancouver Prostate Centre
(författare)
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Getz, GadBroad Institute,Technical University of Denmark
(författare)
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Lawrence, Michael SBroad Institute
(författare)
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Pedersen, Jakob SkouAarhus University Hospital
(författare)
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Rubin, Mark AWeill Cornell Medicine
(författare)
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Wheeler, David ABaylor College of Medicine
(författare)
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Brunak, SørenTechnical University of Denmark
(författare)
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Izarzugaza, Jose M GTechnical University of Denmark
(författare)
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Khurana, EktaWeill Cornell Medical Center
(författare)
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Marchal, KathleenGhent University
(författare)
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von Mering, ChristianUniversity of Zurich
(författare)
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Sahinalp, S CenkVancouver Prostate Centre
(författare)
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Valencia, AlfonsoCentro Nacional de Supercomputación
(författare)
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Stuart, Joshua MUniversity of California, Santa Cruz
(författare)
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Reimand, JüriOntario Institute for Cancer Research
(författare)
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Raphael, Benjamin JPrinceton University
(författare)
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Abascal, FedericoEuropean Bioinformatics Institute
(författare)
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Zou, LihuaNorthwestern University
(författare)
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Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-abo
(creator_code:cre_t)
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Ringnér, MarkusLund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science(Swepub:lu)thep-mri
(creator_code:cre_t)
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Staaf, JohanLund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-jst
(creator_code:cre_t)
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Princeton UniversityUniversity of California, Santa Cruz
(creator_code:org_t)
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PCAWG Drivers and Functional Interpretation Working Group
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PCAWG Consortium
Sammanhörande titlar
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Ingår i:Nature Communications: Springer Science and Business Media LLC112041-1723
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Reyna, Matthew A
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Haan, David
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Paczkowska, Mart ...
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Verbeke, Lieven ...
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Vazquez, Miguel
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Kahraman, Abdull ...
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visa fler...
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Pulido-Tamayo, S ...
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Barenboim, Jonat ...
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Wadi, Lina
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Dhingra, Priyank ...
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Shrestha, Raunak
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Getz, Gad
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Lawrence, Michae ...
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Pedersen, Jakob ...
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Rubin, Mark A
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Wheeler, David A
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Brunak, Søren
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Izarzugaza, Jose ...
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Khurana, Ekta
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Marchal, Kathlee ...
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von Mering, Chri ...
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Sahinalp, S Cenk
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Valencia, Alfons ...
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Stuart, Joshua M
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Reimand, Jüri
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Raphael, Benjami ...
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Abascal, Federic ...
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Zou, Lihua
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Borg, Åke
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Ringnér, Markus
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Staaf, Johan
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