Exome sequencing identifies GRIN2A as frequently mutated in melanoma

XM Wei, V Walia, JC Lin, JK Teer, TD Prickett, J Gartner, S Davis, K Stemke-Hale, MA Davies, JE Gershenwald, W Robinson, S Robinson, SA Rosenberg, Yardena Samuels

Research output: Contribution to journalArticlepeer-review

Abstract

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (∼1/44%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.

Original languageEnglish
Pages (from-to)442-446
Number of pages5
JournalNature Genetics
Volume43
Issue number5
DOIs
StatePublished - May 2011

All Science Journal Classification (ASJC) codes

  • Genetics

Fingerprint

Dive into the research topics of 'Exome sequencing identifies GRIN2A as frequently mutated in melanoma'. Together they form a unique fingerprint.

Cite this