Whole exome sequencing of adenoid cystic carcinoma

P.J. Stephens, H.R. Davies, Y. Mitani, P. Van Loo, A. Shlien, P.S. Tarpey, E. Papaemmanuil, A. Cheverton, G.R. Bignell, A.P. Butler, J. Gamble, S. Gamble, C. Hardy, J. Hinton, M. Jia, A. Jayakumar, D. Jones, C. Latimer, S. McLaren, D.J. McBrideA. Menzies, L. Mudie, M. Maddison, K. Raine, S. Nik-Zainal, S. O'Meara, J.W. Teague, I. Varela, D.C. Wedge, I. Whitmore, S.M. Lippman, U. McDermott, M.R. Stratton, P.J. Campbell, A.K. El-Naggar, P.A. Futreal

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)2965-2968
Number of pages4
JournalJournal of Clinical Investigation
Issue number7
Publication statusPublished - Jul 2013


  • Carcinoma
  • Adenoid cystic carcinoma
  • DNA Mutational Analysis
  • Exome
  • Genes

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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