Open AccessComprehensive evaluation of coding region point mutations in microsatellite‐unstable colorectal cancer
Author(s) -
Kondelin Johanna,
Salokas Kari,
Saarinen Lilli,
Ovaska Kristian,
Rauanheimo Heli,
Plaketti RoosaMaria,
Hamberg Jiri,
Liu Xiaonan,
Yadav Leena,
Gylfe Alexandra E,
Cajuso Tatiana,
Hänninen Ulrika A,
Palin Kimmo,
Ristolainen Heikki,
Katainen Riku,
Kaasinen Eevi,
Tanskanen Tomas,
Aavikko Mervi,
Taipale Minna,
Taipale Jussi,
RenkonenSinisalo Laura,
Lepistö Anna,
Koskensalo Selja,
Böhm Jan,
Mecklin JukkaPekka,
Ongen Halit,
Dermitzakis Emmanouil T,
Kilpivaara Outi,
Vahteristo Pia,
Turunen Mikko,
Hautaniemi Sampsa,
Tuupanen Sari,
Karhu Auli,
Välimäki Niko,
Varjosalo Markku,
Pitkänen Esa,
Aaltonen Lauri A
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708552
Subject(s) - microsatellite , microsatellite instability , colorectal cancer , point mutation , genetics , biology , coding region , coding (social sciences) , computational biology , cancer research , mutation , cancer , gene , mathematics , allele , statistics
Microsatellite instability ( MSI ) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers ( CRC s), 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, MutSig CV . Somatic point mutation data from the exome kit‐targeted area from 24 exome‐sequenced sporadic MSI CRC s and respective normals, and 12 whole‐genome‐sequenced sporadic MSI CRC s and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRC s. The MutSig CV 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, SMARCB 1 and STK 38L , were also functionally scrutinized, providing evidence of a tumorigenic role, for SMARCB 1 mutations in particular.