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

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

British journal of cancer (2014-08-15)
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
PMID25117815
ABSTRACT

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. We utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base-specific somatic mutation hotspots. 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. This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets.