Kondelin , J , Gylfe , A E , Lundgren , S , Tanskanen , T , Hamberg , J , Aavikko , M , Palin , K , Ristolainen , H , Katainen , R , Kaasinen , E , Taipale , M , Taipale , J , Renkonen-Sinisalo , L , Jarvinen , H , Bohm , J , Mecklin , J-P , Vahteristo , P , Tuupanen , S , Aaltonen , L A & Pitkanen , E 2017 , ' Comprehensive Evaluation of Protein Coding Mononucleotide Microsatellites in Microsatellite-Unstable Colorectal Cancer ' , Cancer Research , vol. 77 , no. 15 , pp. 4078-4088 . https://doi.org/10.1158/0008-5472.CAN-17-0682
Title: | Comprehensive Evaluation of Protein Coding Mononucleotide Microsatellites in Microsatellite-Unstable Colorectal Cancer |
Author: | Kondelin, Johanna; Gylfe, Alexandra E.; Lundgren, Sofie; Tanskanen, Tomas; Hamberg, Jiri; Aavikko, Mervi; Palin, Kimmo; Ristolainen, Heikki; Katainen, Riku; Kaasinen, Eevi; Taipale, Minna; Taipale, Jussi; Renkonen-Sinisalo, Laura; Jarvinen, Heikki; Bohm, Jan; Mecklin, Jukka-Pekka; Vahteristo, Pia; Tuupanen, Sari; Aaltonen, Lauri A.; Pitkanen, Esa |
Contributor organization: | Research Programs Unit Genome-Scale Biology (GSB) Research Program Department of Medical and Clinical Genetics Medicum Lauri Antti Aaltonen / Principal Investigator Jussi Taipale / Principal Investigator Clinicum Department of Surgery II kirurgian klinikka Heikki Järvinen / Principal Investigator HUS Abdominal Center |
Date: | 2017-08-01 |
Language: | eng |
Number of pages: | 11 |
Belongs to series: | Cancer Research |
ISSN: | 0008-5472 |
DOI: | https://doi.org/10.1158/0008-5472.CAN-17-0682 |
URI: | http://hdl.handle.net/10138/297913 |
Abstract: | Approximately 15% of colorectal cancers exhibit microsatellite instability (MSI), which leads to accumulation of large numbers of small insertions and deletions (indels). Genes that provide growth advantage to cells via loss-of-function mutations in micro-satellites are called MSI target genes. Several criteria to define these genes have been suggested, one of them being simple mutation frequency. Microsatellite mutation rate, however, depends on the length and nucleotide context of the microsatellite. Therefore, assessing the general impact of mismatch repair deficiency on the likelihood of mutation events is paramount when following this approach. To identify MSI target genes, we developed a statistical model for the somatic background indel mutation rate of microsatellites to assess mutation significance. Exome sequencing data of 24 MSI colorectal cancers revealed indels at 54 million mononucleotide microsatellites of three or more nucleotides in length. The top 105 microsatellites from 71 genes were further analyzed in 93 additional MSI colorectal cancers. Mutation significance and estimated clonality of mutations determined the most likely MSI target genes to be the aminoadipate-semialdehyde dehydrogenase AASDH and the solute transporter SLC9A8. Our findings offer a systematic profiling of the somatic background mutation rate in protein-coding mononucleotide microsatellites, allowing a full cataloging of the true targets of MSI in colorectal cancer. (C) 2017 AACR. |
Subject: |
REPAIR-DEFICIENT CANCERS
DNA MISMATCH REPAIR FRAMESHIFT MUTATIONS TARGET GENES REPEAT SEQUENCES INTESTINAL NHE8 BETA-ALANINE COLON-CANCER INSTABILITY EXPRESSION 3122 Cancers |
Peer reviewed: | Yes |
Rights: | unspecified |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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