Journal Article

Whole exome sequencing of adenoid cystic carcinoma

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

2013

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Biomedical research / Brief Report / Cancer / Carcinoma / Carcinoma, Adenoid Cystic - genetics / DNA Mutational Analysis / DNA sequencing / Exome / Genes / Genes, Neoplasm / Genetic aspects / Genetic Association Studies / High-Throughput Nucleotide Sequencing / Humans / Kinases / Mutation / Nucleotide sequencing / Physiological aspects / Polymorphism, Single Nucleotide / Salivary Gland Neoplasms - genetics / Studies