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

British journal of cancer

PubMedID: 25117815

Tuupanen S, Hänninen UA, Kondelin J, von Nandelstadh P, Cajuso T, Gylfe AE, Katainen R, Tanskanen T, Ristolainen H, Böhm J, Mecklin JP, Järvinen H, Renkonen-Sinisalo L, Andersen CL, Taipale M, Taipale J, Vahteristo P, Lehti K, Pitkänen E, Aaltonen LA. Identification of 33 candidate oncogenes by screening for base-specific mutations. Br J Cancer. 2014;111(8):1657-62.
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.