title: Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations.
abstract: OBJECTIVE
  The majority of adenoid cystic carcinomas (AdCCs), regardless of anatomical site, harbour the MYB-NFIB fusion gene. The aim of this study was to characterize the repertoire of somatic genetic events affecting known cancer genes in AdCCs.
  
  
  RESULTS
  DNA was extracted from 13 microdissected breast AdCCs, and subjected to a mutation survey using the Sequenom OncoCarta Panel v1.0. Genes found to be mutated in any of the breast AdCCs and genes related to the same canonical molecular pathways, as well as KIT, a proto-oncogene whose protein product is expressed in AdCCs, were sequenced in an additional 68 AdCCs from various anatomical sites by Sanger sequencing. Using the Sequenom MassARRAY platform and Sanger sequencing, mutations in BRAF and HRAS were identified in three and one cases, respectively (breast, and head and neck). KIT, which has previously been reported to be mutated in AdCCs, was also investigated, but no mutations were identified.
  
  
  CONCLUSIONS
  Our results demonstrate that mutations in genes pertaining to the canonical RAS pathway are found in a minority of AdCCs, and that activating KIT mutations are either absent or remarkably rare in these cancers, and unlikely to constitute a driver and therapeutic target for patients with AdCC.
authors: The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
authors: Daniel
authors: D
authors: Wetterskog
authors: Paul M
authors: PM
authors: Wilkerson
authors: Daniel N
authors: DN
authors: Rodrigues
authors: Maryou B
authors: MB
authors: Lambros
authors: Karen
authors: K
authors: Fritchie
authors: Mattias K
authors: MK
authors: Andersson
authors: Rachael
authors: R
authors: Natrajan
authors: Arnaud
authors: A
authors: Gauthier
authors: Silvana
authors: S
authors: Di Palma
authors: Sami
authors: S
authors: Shousha
authors: Zoran
authors: Z
authors: Gatalica
authors: Chantal
authors: C
authors: Töpfer
authors: Vesna
authors: V
authors: Vukovic
authors: Roger
authors: R
authors: A'Hern
authors: Britta
authors: B
authors: Weigelt
authors: Anne
authors: A
authors: Vincent-Salomon
authors: Göran
authors: G
authors: Stenman
authors: Brian P
authors: BP
authors: Rubin
authors: Jorge S
authors: JS
authors: Reis-Filho
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
references: Oncogene. 2011 Aug 11;30(32):3477-88
references: 21577205
references: J Pathol. 2004 Mar;202(3):375-81
references: 14991904
references: Cancer Lett. 2000 Jun 1;154(1):107-11
references: 10799746
references: Mol Cancer. 2009 Oct 08;8:82
references: 19811662
references: Anticancer Res. 2003 May-Jun;23(3B):2735-40
references: 12894567
references: Oral Oncol. 2009 Sep;45(9):826-9
references: 19362042
references: J Pathol. 2010 Nov;222(3):282-98
references: 20815046
references: Nat Med. 2006 Jul;12(7):852-5
references: 16799556
references: J Pathol. 2008 Oct;216(2):141-50
references: 18720457
references: Oral Oncol. 2007 Sep;43(8):735-41
references: 17113340
references: Nature. 2012 May 16;486(7403):400-4
references: 22722201
references: Clin Cancer Res. 2010 Oct 1;16(19):4722-31
references: 20702610
references: Oncol Rep. 2009 May;21(5):1215-22
references: 19360297
references: Nat Rev Cancer. 2003 Jan;3(1):11-22
references: 12509763
references: Lab Invest. 2008 May;88(5):464-73
references: 18332873
references: J Clin Oncol. 2005 Sep 1;23(25):6271-3; author reply 6273-4
references: 16135502
references: Oral Oncol. 2002 Oct;38(7):706-13
references: 12167424
references: Semin Diagn Pathol. 2003 Nov;20(4):279-304
references: 14694981
references: Am J Surg Pathol. 2011 Jan;35(1):92-9
references: 21164292
references: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14903-8
references: 20668238
references: Genes Chromosomes Cancer. 2012 Aug;51(8):805-17
references: 22505352
references: Mod Pathol. 2009 Oct;22(10):1296-302
references: 19617878
references: Blood. 2000 Aug 1;96(3):925-32
references: 10910906
references: Cancer. 2007 Dec 1;110(11):2507-10
references: 17932891
references: J Pathol. 2012 Jan;226(1):84-96
references: 22015727
references: Head Neck. 2005 Dec;27(12):1022-7
references: 16265655
references: Nature. 2002 Jun 27;417(6892):949-54
references: 12068308
references: Head Neck. 2004 Sep;26(9):829-31
references: 15350030
references: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18740-4
references: 19841262
references: Mod Pathol. 2011 Feb;24(2):209-31
references: 21076461
references: Hum Pathol. 2007 Sep;38(9):1425-31
references: 17669465
references: Mod Pathol. 2011 Sep;24(9):1169-76
references: 21572406
references: Pharmacogenomics. 2010 Apr;11(4):559-71
references: 20350138
references: Cell. 2010 Jan 22;140(2):209-21
references: 20141835
references: Cell. 2004 Mar 19;116(6):855-67
references: 15035987
references: PLoS One. 2009 Nov 18;4(11):e7887
references: 19924296
references: Nature. 2010 Sep 30;467(7315):596-9
references: 20823850
references: Mod Pathol. 1999 Oct;12(10):956-60
references: 10530560
references: J Clin Oncol. 2005 Jan 20;23(3):585-90
references: 15659505
references: BMC Cancer. 2010 Mar 16;10:101
references: 20233444
references: Neoplasia. 2010 Sep;12(9):708-17
references: 20824047
references: Mol Cell Biol. 2010 Feb;30(3):806-19
references: 19933846
references: J Clin Pathol. 2010 Mar;63(3):220-8
references: 20203221
references: Cancer. 2002 Apr 15;94(8):2119-27
references: 12001107
references: Cancer Res. 2003 Dec 1;63(23):8132-7
references: 14678966