Comprehensive evaluation of coding region point mutations in microsatellite‐unstable colorectal cancer
Year: 2018
Type: article
Study design: Observational Study
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.
Source: EMBO Molecular Medicine
Authors: Johanna Kondelin, Kari Salokas, Lilli Saarinen, Kristian Ovaska, Heli Rauanheimo, Roosa‐Maria Plaketti, Jiri Hamberg, Xiaonan Liu, Leena Yadav, Alexandra E Gylfe, Tatiana Cajuso, Ulrika A Hänninen, Kimmo Palin, Heikki Ristolainen, Riku Katainen, Eevi Kaasinen, Tomas Tanskanen, Mervi Aavikko, Minna Taipale, Jussi Taipale, Laura Renkonen‐Sinisalo, Anna Lepistö, Selja Koskensalo, Jan Böhm, Jukka‐Pekka Mecklin, Halit Ongen, Emmanouil T Dermitzakis, Outi Kilpivaara, Pia Vahteristo, Mikko Turunen, Sampsa Hautaniemi, Sari Tuupanen, Auli Karhu, Niko Välimäki, Markku Varjosalo, Esa Pitkänen, Lauri A Aaltonen
Institutions: University of Helsinki, HiLIFE – Elämäntieteiden Instituutti, Karolinska Institutet, Helsinki University Hospital, Hospital District of Helsinki and Uusimaa, Central Finland Health Care District, University of Eastern Finland, University of Jyväskylä, University of Geneva, SIB Swiss Institute of Bioinformatics, Institute of Genetics and Genomics in Geneva
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: Ida Montinin Säätiö, Helsingin Yliopisto, Maud Kuistilan Muistosäätiö, Wellcome Trust, Academy of Finland, Biomedicum Helsinki-säätiö, Jane ja Aatos Erkon Säätiö, China Scholarship Council, Emil Aaltosen Säätiö, Samfundet Folkhälsan, Oskar Öflunds Stiftelse, Orionin Tutkimussäätiö, Otto A. Malm Lahjoitusrahasto, Helsinki Institute of Life Science, Helsingin Yliopisto, National Heart, Lung, and Blood Institute
OpenAlex ID: W2887729068