Contribution of allelic imbalance to colorectal cancer

Show simple item record Palin, Kimmo Pitkänen, Esa Turunen, Mikko Sahu, Biswajyoti Pihlajamaa, Päivi Kivioja, Teemu Kaasinen, Eevi Välimäki, Niko Hänninen, Ulrika A. Cajuso, Tatiana Aavikko, Mervi Tuupanen, Sari Kilpivaara, Outi van den Berg, Linda Kondelin, Johanna Tanskanen, Tomas Katainen, Riku Grau, Marta Rauanheimo, Heli Plaketti, Roosa-Maria Taira, Aurora Sulo, Päivi Hartonen, Tuomo Dave, Kashyap Schmierer, Bernhard Botla, Sandeep Sokolova, Maria Vähärautio, Anna Gladysz, Kornelia Ongen, Halit Dermitzakis, Emmanouil Bramsen, Jesper Bertram Orntoft, Torben Falck Andersen, Claus Lindbjerg Ristimäki, Ari Lepistö, Anna Renkonen-Sinisalo, Laura Mecklin, Jukka-Pekka Taipale, Jussi Aaltonen, Lauri A. 2018-10-05T06:31:01Z 2018-10-05T06:31:01Z 2018-09-10
dc.identifier.citation Palin , K , Pitkänen , E , Turunen , M , Sahu , B , Pihlajamaa , P , Kivioja , T , Kaasinen , E , Välimäki , N , Hänninen , U A , Cajuso , T , Aavikko , M , Tuupanen , S , Kilpivaara , O , van den Berg , L , Kondelin , J , Tanskanen , T , Katainen , R , Grau , M , Rauanheimo , H , Plaketti , R-M , Taira , A , Sulo , P , Hartonen , T , Dave , K , Schmierer , B , Botla , S , Sokolova , M , Vähärautio , A , Gladysz , K , Ongen , H , Dermitzakis , E , Bramsen , J B , Orntoft , T F , Andersen , C L , Ristimäki , A , Lepistö , A , Renkonen-Sinisalo , L , Mecklin , J-P , Taipale , J & Aaltonen , L A 2018 , ' Contribution of allelic imbalance to colorectal cancer ' , Nature Communications , vol. 9 , 3664 .
dc.identifier.other PURE: 116428914
dc.identifier.other PURE UUID: d71e2d42-6fcd-41ae-bc47-0bbf3d35b633
dc.identifier.other WOS: 000444078300007
dc.identifier.other Scopus: 85053197758
dc.identifier.other ORCID: /0000-0001-6576-5440/work/49156899
dc.identifier.other ORCID: /0000-0003-4721-3954/work/49158607
dc.identifier.other ORCID: /0000-0002-5866-4059/work/49162394
dc.identifier.other ORCID: /0000-0001-5965-8518/work/49162696
dc.identifier.other ORCID: /0000-0002-1333-8049/work/91815955
dc.identifier.other ORCID: /0000-0001-6839-4286/work/101502577
dc.description.abstract Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (Al) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible Al targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within Al peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of Al. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between Al target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of Al in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers. en
dc.format.extent 9
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject HUMAN-COLON
dc.subject GENOME
dc.subject CELLS
dc.subject ENHANCERS
dc.subject GENES
dc.subject 3111 Biomedicine
dc.title Contribution of allelic imbalance to colorectal cancer en
dc.type Article
dc.contributor.organization Research Programs Unit
dc.contributor.organization Lauri Antti Aaltonen / Principal Investigator
dc.contributor.organization Genome-Scale Biology (GSB) Research Program
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Medicum
dc.contributor.organization University of Helsinki
dc.contributor.organization Doctoral Programme in Integrative Life Science
dc.contributor.organization Centre of Excellence in Stem Cell Metabolism
dc.contributor.organization Nutrient sensing laboratory
dc.contributor.organization Jussi Taipale / Principal Investigator
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Department of Pathology
dc.contributor.organization HUSLAB
dc.contributor.organization Gastrointestinal tumorigenesis
dc.contributor.organization Clinicum
dc.contributor.organization Doctoral Programme in Clinical Research
dc.contributor.organization Department of Surgery
dc.contributor.organization II kirurgian klinikka
dc.contributor.organization HUS Abdominal Center
dc.description.reviewstatus Peer reviewed
dc.relation.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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