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Br J Cancer. 2014 Oct 14;111(8):1657-62. doi: 10.1038/bjc.2014.429. Epub 2014 Aug 12.

Identification of 33 candidate oncogenes by screening for base-specific mutations.

Author information

1
1] Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki 00014, Finland [2] Research Programs Unit, Genome-Scale Biology Research Program, University of Helsinki, Biomedicum, PO Box 63 (Haartmaninkatu 8), Helsinki FIN-00014, Finland.
2
Research Programs Unit, Genome-Scale Biology Research Program, University of Helsinki, Biomedicum, PO Box 63 (Haartmaninkatu 8), Helsinki FIN-00014, Finland.
3
Department of Pathology, Jyväskylä Central Hospital, University of Eastern Finland, Keskussairaalantie 19, Jyväskylä 40620, Finland.
4
Department of Surgery, Jyväskylä Central Hospital, University of Eastern Finland, Keskussairaalantie 19, Jyväskylä 40620, Finland.
5
Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki 00290, Finland.
6
Department for Molecular Medicine (MOMA), Aarhus University Hospital, Brendstrupgårdsvej 21, Aarhus N DK-8200, Denmark.
7
1] Research Programs Unit, Genome-Scale Biology Research Program, University of Helsinki, Biomedicum, PO Box 63 (Haartmaninkatu 8), Helsinki FIN-00014, Finland [2] Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, Huddinge SE-141 83, Sweden.

Abstract

BACKGROUND:

Genes with recurrent codon-specific somatic mutations are likely drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers may represent a sensitive system for generation and selection of oncogenic mutations.

METHODS:

We utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base-specific somatic mutation hotspots.

RESULTS:

We identified novel mutation hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of 254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the hotspot mutations in multiple cancer types.

CONCLUSIONS:

This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets.

PMID:
25117815
PMCID:
PMC4200084
DOI:
10.1038/bjc.2014.429
[Indexed for MEDLINE]
Free PMC Article

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