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Exome sequencing reveals frequent inactivating mutations in ARID1A, ARID1B, ARID2 and ARID4A in microsatellite unstable colorectal cancer
Author(s) -
Cajuso Tatiana,
Hänninen Ulrika A.,
Kondelin Johanna,
Gylfe Alexandra E.,
Tanskanen Tomas,
Katainen Riku,
Pitkänen Esa,
Ristolainen Heikki,
Kaasinen Eevi,
Taipale Minna,
Taipale Jussi,
Böhm Jan,
RenkonenSinisalo Laura,
Mecklin JukkaPekka,
Järvinen Heikki,
Tuupanen Sari,
Kilpivaara Outi,
Vahteristo Pia
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28705
Subject(s) - arid1a , biology , exome sequencing , genetics , gene , mutation , exome , chromatin remodeling , cancer , cancer research , chromatin
ARID1A has been identified as a novel tumor suppressor gene in ovarian cancer and subsequently in various other tumor types. ARID1A belongs to the ARID domain containing gene family, which comprises of 15 genes involved, for example, in transcriptional regulation, proliferation and chromatin remodeling. In this study, we used exome sequencing data to analyze the mutation frequency of all the ARID domain containing genes in 25 microsatellite unstable (MSI) colorectal cancers (CRCs) as a first systematic effort to characterize the mutation pattern of the whole ARID gene family. Genes which fulfilled the selection criteria in this discovery set (mutations in at least 4/25 [16%] samples, including at least one nonsense or splice site mutation) were chosen for further analysis in an independent validation set of 21 MSI CRCs. We found that in addition to ARID1A , which was mutated in 39% of the tumors (18/46), also ARID1B (13%, 6/46), ARID2 (13%, 6/46) and ARID4A (20%, 9/46) were frequently mutated. In all these genes, the mutations were distributed along the entire length of the gene, thus distinguishing them from typical MSI target genes previously described. Our results indicate that in addition to ARID1A , other members of the ARID gene family may play a role in MSI CRC.