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

S Tuupanen; U A Hänninen; J Kondelin; P von Nandelstadh; T Cajuso; A E Gylfe; R Katainen; T Tanskanen; H Ristolainen; J Böhm; J-P Mecklin; H Järvinen; L Renkonen-Sinisalo; C L Andersen; M Taipale; J Taipale; P Vahteristo; K Lehti; E Pitkänen; L A Aaltonen

doi:10.1038/bjc.2014.429

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

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

Authors

S Tuupanen¹, U A Hänninen¹, J Kondelin¹, P von Nandelstadh², T Cajuso¹, A E Gylfe¹, R Katainen¹, T Tanskanen¹, H Ristolainen¹, J Böhm³, J-P Mecklin⁴, H Järvinen⁵, L Renkonen-Sinisalo⁵, C L Andersen⁶, M Taipale⁷, J Taipale⁷, P Vahteristo¹, K Lehti², E Pitkänen¹, L A Aaltonen¹

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Microsatellite Instability
Mutation*
Neoplasms / genetics
Oncogenes*