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

J. Kondelin, K. Salokas, L. Saarinen, K. Ovaska, H. Rauanheimo, R.-M. Plaketti, J. Hamberg, X. Liu, L. Yadav, A.E. Gylfe, T. Cajuso, U.A. Hänninen, K. Palin, H. Ristolainen, R. Katainen, E. Kaasinen, T. Tanskanen, M. Aavikko, M. Taipale, J. TaipaleL. Renkonen-Sinisalo, A. Lepistö, S. Koskensalo, J. Böhm, J.-P. Mecklin, H. Ongen, E.T. Dermitzakis, O. Kilpivaara, P. Vahteristo, M. Turunen, S. Hautaniemi, S. Tuupanen, A. Karhu, N. Välimäki, M. Varjosalo, E. Pitkänen, L.A. Aaltonen

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review


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
TidskriftEMBO molecular medicine
Antal sidor20
StatusPublicerad - 2018
MoE-publikationstypA1 Tidskriftsartikel-refererad


  • 3111 Biomedicinska vetenskaper
  • 1184 Genetik, utvecklingsbiologi, fysiologi
  • 3122 Cancersjukdomar

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