Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer

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Kondelin , J , Salokas , K , Saarinen , L , Ovaska , K , Rauanheimo , H , Plaketti , R-M , Hamberg , J , Liu , X , Yadav , L , Gylfe , A E , Cajuso , T , Hänninen , U A , Palin , K , Ristolainen , H , Katainen , R , Kaasinen , E , Tanskanen , T , Aavikko , M , Taipale , M , Taipale , J , Renkonen-Sinisalo , L , Lepistö , A , Koskensalo , S , Böhm , J , Mecklin , J-P , Ongen , H , Dermitzakis , E T , Kilpivaara , O , Vahteristo , P , Turunen , M , Hautaniemi , S , Tuupanen , S , Karhu , A , Välimäki , N , Varjosalo , M , Pitkänen , E & Aaltonen , L A 2018 , ' Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer ' , EMBO molecular medicine , vol. 10 , no. 9 , e8552 .

Title: Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer
Author: Kondelin, J.; Salokas, K.; Saarinen, L.; Ovaska, K.; Rauanheimo, H.; Plaketti, R.-M.; Hamberg, J.; Liu, X.; Yadav, L.; Gylfe, A.E.; Cajuso, T.; Hänninen, U.A.; Palin, K.; Ristolainen, H.; Katainen, R.; Kaasinen, E.; Tanskanen, T.; Aavikko, M.; Taipale, M.; Taipale, J.; Renkonen-Sinisalo, L.; Lepistö, A.; Koskensalo, S.; Böhm, J.; Mecklin, J.-P.; Ongen, H.; Dermitzakis, E.T.; Kilpivaara, O.; Vahteristo, P.; Turunen, M.; Hautaniemi, S.; Tuupanen, S.; Karhu, A.; Välimäki, N.; Varjosalo, M.; Pitkänen, E.; Aaltonen, L.A.
Contributor organization: Lauri Antti Aaltonen / Principal Investigator
Genome-Scale Biology (GSB) Research Program
Department of Medical and Clinical Genetics
Institute of Biotechnology
Department of Surgery
Department of Biochemistry and Developmental Biology
Sampsa Hautaniemi / Principal Investigator
Molecular Systems Biology
HUS Abdominal Center
Date: 2018
Language: eng
Number of pages: 20
Belongs to series: EMBO molecular medicine
ISSN: 1757-4676
Abstract: Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs. The MutSigCV ranking identified several well-established MSI CRC driver genes and provided additional evidence for previously proposed CRC candidate genes as well as shortlisted genes that have to our knowledge not been linked to CRC before. Two genes, SMARCB1 and STK38L, were also functionally scrutinized, providing evidence of a tumorigenic role, for SMARCB1 mutations in particular. © 2018 The Authors. Published under the terms of the CC BY 4.0 license
Subject: Article
cancer cell
clinical evaluation
colony formation
colorectal cancer
controlled study
gene expression
gene frequency
gene interaction
gene replication
genetic analysis
genetic code
genetic identification
human cell
human tissue
microsatellite instability
mutator gene
point mutation
priority journal
R105W gene
single nucleotide polymorphism
SMARCB1 gene
STK38L gene
tumor-related gene
validation process
whole exome sequencing
wild type
3111 Biomedicine
1184 Genetics, developmental biology, physiology
3122 Cancers
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion

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