title: Whole exome sequencing of adenoid cystic carcinoma.
abstract: 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.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: Helen R
authors.initials: HR
authors.lastname: Davies
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Mitani
authors.forename: Peter
authors.initials: P
authors.lastname: Van Loo
authors.forename: Adam
authors.initials: A
authors.lastname: Shlien
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tarpey
authors.forename: Elli
authors.initials: E
authors.lastname: Papaemmanuil
authors.forename: Angela
authors.initials: A
authors.lastname: Cheverton
authors.forename: Graham R
authors.initials: GR
authors.lastname: Bignell
authors.forename: Adam P
authors.initials: AP
authors.lastname: Butler
authors.forename: John
authors.initials: J
authors.lastname: Gamble
authors.forename: Stephen
authors.initials: S
authors.lastname: Gamble
authors.forename: Claire
authors.initials: C
authors.lastname: Hardy
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hinton
authors.forename: Mingming
authors.initials: M
authors.lastname: Jia
authors.forename: Alagu
authors.initials: A
authors.lastname: Jayakumar
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.forename: Calli
authors.initials: C
authors.lastname: Latimer
authors.forename: Stuart
authors.initials: S
authors.lastname: McLaren
authors.forename: David J
authors.initials: DJ
authors.lastname: McBride
authors.forename: Andrew
authors.initials: A
authors.lastname: Menzies
authors.forename: Laura
authors.initials: L
authors.lastname: Mudie
authors.forename: Mark
authors.initials: M
authors.lastname: Maddison
authors.forename: Keiran
authors.initials: K
authors.lastname: Raine
authors.forename: Serena
authors.initials: S
authors.lastname: Nik-Zainal
authors.forename: Sarah
authors.initials: S
authors.lastname: O'Meara
authors.forename: Jon W
authors.initials: JW
authors.lastname: Teague
authors.forename: Ignacio
authors.initials: I
authors.lastname: Varela
authors.forename: David C
authors.initials: DC
authors.lastname: Wedge
authors.forename: Ian
authors.initials: I
authors.lastname: Whitmore
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Ultan
authors.initials: U
authors.lastname: McDermott
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
mesh_terms: D003528:Carcinoma, Adenoid Cystic / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D052138:Genes, Neoplasm; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012468:Salivary Gland Neoplasms / Q000235:genetics*