Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Whole exome sequencing of adenoid cystic carcinoma

2013; American Society for Clinical Investigation; Volume: 123; Issue: 7 Linguagem: Inglês

10.1172/jci67201

1558-8238

Philip J. Stephens, Helen Davies, Yoshitsugu Mitani, Peter Van Loo, Adam Shlien, Patrick Tarpey, Elli Papaemmanuil, Angela Cheverton, Graham R. Bignell, Adam P. Butler, John Gamble, Stephen J. Gamble, Claire Hardy, Jonathan Hinton, Mingming Jia, Alagu Jayakumar, David Jones, Calli Latimer, Stuart McLaren, David J. McBride, Andrew Menzies, Laura Mudie, Mark Maddison, Keiran Raine, Serena Nik‐Zainal, Sarah O’Meara, Jon W. Teague, Ignacio Varela, David C. Wedge, Ian Whitmore, Scott M. Lippman, Ultan McDermott, Michael R. Stratton, Peter J. Campbell, Adel K. El‐Naggar, P. Andrew Futreal,

Tumors and Oncological Cases

Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.