Contribution of allelic imbalance to colorectal cancer

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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 . https://doi.org/10.1038/s41467-018-06132-1

Title: Contribution of allelic imbalance to colorectal cancer
Author: 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.
Contributor organization: Research Programs Unit
Lauri Antti Aaltonen / Principal Investigator
Genome-Scale Biology (GSB) Research Program
Department of Medical and Clinical Genetics
Medicum
University of Helsinki
Doctoral Programme in Integrative Life Science
Centre of Excellence in Stem Cell Metabolism
Nutrient sensing laboratory
Jussi Taipale / Principal Investigator
Institute of Biotechnology
Department of Pathology
HUSLAB
Gastrointestinal tumorigenesis
Clinicum
Doctoral Programme in Clinical Research
Department of Surgery
II kirurgian klinikka
HUS Abdominal Center
Date: 2018-09-10
Language: eng
Number of pages: 9
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-06132-1
URI: http://hdl.handle.net/10138/247091
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.
Subject: HUMAN-COLON
GENOME
CELLS
ENHANCERS
GENES
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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