title: Comprehensive genomic characterization of head and neck squamous cell carcinomas.
abstract: The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D014157:Transcription Factors
references: Cancer Cell. 2004 May;5(5):489-500
references: 15144956
references: Science. 2011 Aug 26;333(6046):1157-60
references: 21798893
references: Cancer Res. 2013 Jul 15;73(14):4289-99
references: 23722545
references: Nature. 2006 Jan 12;439(7073):208-11
references: 16306936
references: Science. 2011 Aug 26;333(6046):1154-7
references: 21798897
references: J Cell Biol. 2011 Nov 28;195(5):855-71
references: 22105346
references: Cell Oncol. 2009;31(4):291-300
references: 19633365
references: Nat Genet. 2013 Mar;45(3):253-61
references: 23354438
references: Oncogene. 1996 Nov 21;13(10):2243-54
references: 8950992
references: Nat Cell Biol. 2007 Jul;9(7):804-12
references: 17589499
references: Biochem Biophys Res Commun. 2001 Oct 12;287(5):1140-7
references: 11587542
references: Curr Protoc Hum Genet. 2008 Apr;Chapter 10:Unit 10.11
references: 18428421
references: PLoS One. 2013;8(2):e56823
references: 23451093
references: Nat Rev Mol Cell Biol. 2011 Oct 21;12(11):757-63
references: 22016059
references: Cell Cycle. 2011 Sep 15;10(18):3086-94
references: 21900750
references: Br J Cancer. 1995 Aug;72(2):405-11
references: 7640226
references: Nucleic Acids Res. 2001 Jan 1;29(1):308-11
references: 11125122
references: J Pathol. 2013 Nov;231(3):311-22
references: 23868181
references: Genes Dev. 2006 May 15;20(10):1331-42
references: 16702406
references: Nat Genet. 2013 Oct;45(10):1127-33
references: 24071851
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: Science. 1997 Dec 5;278(5344):1812-5
references: 9388187
references: N Engl J Med. 2010 Jul 1;363(1):24-35
references: 20530316
references: Biochem Biophys Res Commun. 2010 Jun 11;396(4):887-93
references: 20457130
references: Br J Cancer. 1990 Dec;62(6):1047-51
references: 2257212
references: Cancer Res. 2011 May 15;71(10):3688-700
references: 21576089
references: Cell Cycle. 2013 May 1;12(9):1340-51
references: 23574746
references: Nat Rev Cancer. 2009 Aug;9(8):587-95
references: 19609265
references: Nature. 2013 Jul 4;499(7456):43-9
references: 23792563
references: J Invest Dermatol. 2013 Jan;133(1):239-48
references: 22832494
references: Cytogenet Cell Genet. 1987;44(1):58-62
references: 3028716
references: Clin Cancer Res. 2013 Jan 1;19(1):279-90
references: 23091115
references: PLoS Pathog. 2013;9(5):e1003384
references: 23717208
references: Am J Med Genet A. 2011 Sep;155A(9):2105-11
references: 21834047
references: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10395-9
references: 10984535
references: Dev Cell. 2013 Mar 11;24(5):459-71
references: 23484853
references: Nature. 2012 Sep 27;489(7417):519-25
references: 22960745
references: Cancer Res. 2006 Jan 1;66(1):283-9
references: 16397241
references: Cancer Cell. 2007 Aug;12(2):115-30
references: 17692804
references: Sci Signal. 2013 Sep 10;6(292):ra81
references: 24023255
references: Int J Cancer. 2002 Jun 1;99(4):538-48
references: 11992543
references: J Virol. 2011 Mar;85(5):2189-200
references: 21177803
references: Oncogene. 2008 Jan 10;27(3):274-84
references: 17621269
references: Clin Cancer Res. 2006 Sep 1;12(17):5064-73
references: 16951222
references: Front Genet. 2013 May 28;4:95
references: 23755068