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Pathway and network...
Pathway and network analysis of more than 2500 whole cancer genomes
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- Reyna, Matthew A (author)
- Princeton University
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- Haan, David (author)
- University of California, Santa Cruz
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- Paczkowska, Marta (author)
- Ontario Institute for Cancer Research
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- Verbeke, Lieven P C (author)
- Ghent University
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- Vazquez, Miguel (author)
- Centro Nacional de Supercomputación
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- Kahraman, Abdullah (author)
- University of Zurich
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- Pulido-Tamayo, Sergio (author)
- Ghent University
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- Barenboim, Jonathan (author)
- Ontario Institute for Cancer Research
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- Wadi, Lina (author)
- Ontario Institute for Cancer Research
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- Dhingra, Priyanka (author)
- Weill Cornell Medicine
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- Shrestha, Raunak (author)
- Vancouver Prostate Centre
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- Getz, Gad (author)
- Broad Institute,Technical University of Denmark
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- Lawrence, Michael S (author)
- Broad Institute
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- Pedersen, Jakob Skou (author)
- Aarhus University Hospital
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- Rubin, Mark A (author)
- Weill Cornell Medicine
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- Wheeler, David A (author)
- Baylor College of Medicine
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- Brunak, Søren (author)
- Technical University of Denmark
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- Izarzugaza, Jose M G (author)
- Technical University of Denmark
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- Khurana, Ekta (author)
- Weill Cornell Medical Center
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- Marchal, Kathleen (author)
- Ghent University
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- von Mering, Christian (author)
- University of Zurich
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- Sahinalp, S Cenk (author)
- Vancouver Prostate Centre
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- Valencia, Alfonso (author)
- Centro Nacional de Supercomputación
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- Stuart, Joshua M (author)
- University of California, Santa Cruz
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- Reimand, Jüri (author)
- Ontario Institute for Cancer Research
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- Raphael, Benjamin J (author)
- Princeton University
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- Abascal, Federico (author)
- European Bioinformatics Institute
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- Zou, Lihua (author)
- Northwestern University
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- Borg, Åke (creator_code:cre_t)
- Lund 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
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- Ringnér, Markus (creator_code:cre_t)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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- Staaf, Johan (creator_code:cre_t)
- Lund 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
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- 2020-02-05
- 2020
- English 17 s.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Chromatin Assembly and Disassembly
- Computational Biology/methods
- Databases, Genetic
- Gene Expression Regulation, Neoplastic
- Genome, Human
- Humans
- Metabolic Networks and Pathways/genetics
- Mutation
- Neoplasms/genetics
- Promoter Regions, Genetic
- RNA Splicing
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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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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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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Uppsala University
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Karolinska Institutet