title: Unraveling the molecular genetics of head and neck cancer through genome-wide approaches.
abstract: The past decade has seen an unprecedented increase in our understanding of the biology and etiology of head and neck squamous cell carcinomas (HNSCC). Genome-wide sequencing projects have identified a number of recurrently mutated genes, including unexpected alterations in the NOTCH pathway and chromatin related genes. Gene-expression profiling has identified 4 distinct genetic subtypes which show some parallels to lung squamous cell carcinoma biology. The identification of the human papilloma virus as one causative agent in a subset of oropharyngeal cancers and their association with a favorable prognosis has opened up avenues for new therapeutic strategies. The expanding knowledge of the underlying molecular abnormalities in this once very poorly understood cancer should allow for increasingly rational clinical trial design and improved patient outcomes.
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Nadeem
authors: N
authors: Riaz
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Luc G
authors: LG
authors: Morris
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: William
authors: W
authors: Lee
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA ; Department of Human Oncology and Pathogenesis, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Timothy A
authors: TA
authors: Chan
keywords: Copy number; Gene expression; Genomics; Head and neck cancer; Mutation
references: Ann Oncol. 2011 May;22(5):1078-1087
references: 21048039
references: Cancer Metastasis Rev. 2005 Jan;24(1):47-69
references: 15785872
references: PLoS One. 2013;8(2):e56823
references: 23451093
references: Sci Transl Med. 2011 Sep 7;3(99):99ra86
references: 21900593
references: Int J Cancer. 2013 Apr 15;132(8):1781-9
references: 22987500
references: Annu Rev Genet. 2009;43:223-49
references: 19686080
references: Nat Rev Cancer. 2007 Nov;7(11):823-33
references: 17957188
references: Head Neck. 2013 Mar;35(3):454-63
references: 22907887
references: Am J Hum Genet. 2012 Mar 9;90(3):511-7
references: 22341969
references: Arch Otolaryngol Head Neck Surg. 1995 Feb;121(2):157-60
references: 7840922
references: Nat Rev Cancer. 2003 Feb;3(2):117-29
references: 12563311
references: Mol Ther. 2013 Jan;21(1):91-100
references: 22990672
references: Lancet Oncol. 2013 Jul;14(8):697-710
references: 23746666
references: Cancer Cell. 2004 May;5(5):489-500
references: 15144956
references: Cell. 2012 Jul 6;150(1):12-27
references: 22770212
references: Int J Cancer. 2009 Jan 15;124(2):394-401
references: 18814262
references: Haematologica. 2008 Apr;93(4):511-7
references: 18322251
references: Cancer Res. 1993 Aug 1;53(15):3579-84
references: 8339264
references: Cancer Lett. 2011 Jul 28;306(2):134-41
references: 21411222
references: Science. 2004 Oct 8;306(5694):269-71
references: 15472075
references: J Clin Oncol. 2013 Apr 10;31(11):1415-21
references: 23460709
references: J Natl Cancer Inst. 2005 Jul 20;97(14):1043-55
references: 16030302
references: Head Neck Pathol. 2012 Jul;6 Suppl 1:S3-15
references: 22782219
references: Br J Cancer. 2010 Jan 19;102(2):428-35
references: 20087356
references: J Clin Oncol. 2006 Jun 10;24(17):2666-72
references: 16763281
references: Nat Rev Cancer. 2005 May;5(5):341-54
references: 15864276
references: Int J Cancer. 2007 Apr 15;120(8):1731-8
references: 17236202
references: J Clin Oncol. 2007 Jun 1;25(16):2164-70
references: 17538160
references: Science. 2011 Aug 26;333(6046):1157-60
references: 21798893
references: Radiother Oncol. 1998 Feb;46(2):135-46
references: 9510041
references: Clin Cancer Res. 2013 Apr 1;19(7):1858-72
references: 23444227
references: Radiother Oncol. 2002 Mar;62(3):345-7
references: 12175566
references: Nat Rev Cancer. 2009 Aug;9(8):550-62
references: 19629070
references: Acta Otorhinolaryngol Ital. 2012 Feb;32(1):1-11
references: 22500060
references: Cancer Cell. 2010 Jan 19;17(1):98-110
references: 20129251
references: Genes Dev. 2013 Oct 15;27(20):2179-91
references: 24142871
references: Cell Cycle. 2013 Apr 1;12(7):1011-2
references: 23493187
references: Cancer Sci. 2008 Aug;99(8):1507-14
references: 18754860
references: Clin Cancer Res. 2007 Sep 1;13(17):4964-73
references: 17785546
references: Oral Oncol. 2014 Mar;50(3):178-88
references: 24370206
references: Nat Rev Mol Cell Biol. 2010 Mar;11(3):220-8
references: 20177397
references: N Engl J Med. 2007 May 10;356(19):1944-56
references: 17494927
references: J Clin Oncol. 2013 Apr 10;31(11):1381-3
references: 23460713
references: Toxicol Pathol. 2007 Jun;35(4):495-516
references: 17562483
references: Head Neck. 1998 Mar;20(2):145-51
references: 9484946
references: Oncogene. 2003 Feb 27;22(8):1225-37
references: 12606949
references: Cancer Res. 2008 Mar 1;68(5):1303-9
references: 18316592
references: Cancer Res. 2002 Dec 15;62(24):7350-6
references: 12499279
references: Nat Commun. 2013;4:2873
references: 24292195
references: Head Neck. 2006 Sep;28(9):813-8
references: 16637057
references: N Engl J Med. 2008 Mar 13;358(11):1160-74
references: 18337605
references: Science. 2011 Aug 26;333(6046):1154-7
references: 21798897
references: Oncogene. 2008 Sep 1;27(38):5115-23
references: 18758480
references: BMJ. 1996 Sep 21;313(7059):716-21
references: 8819440
references: Oral Oncol. 2011 Sep;47(9):783-91
references: 21802978
references: Lancet Oncol. 2010 Jan;11(1):21-8
references: 19897418
references: Nature. 2000 Aug 17;406(6797):747-52
references: 10963602
references: Hum Pathol. 1999 Oct;30(10):1221-5
references: 10534171
references: Clin Cancer Res. 2014 Jun 1;20(11):2873-84
references: 24668645
references: Nat Rev Cancer. 2011 Jan;11(1):9-22
references: 21160525
references: J Clin Oncol. 2011 Nov 10;29(32):4294-301
references: 21969503
references: Expert Opin Ther Targets. 2005 Aug;9(4):769-90
references: 16083342
references: Clin Cancer Res. 2011 Jun 1;17(11):3733-41
references: 21467160
references: Cell Oncol. 2009;31(4):291-300
references: 19633365
references: N Engl J Med. 2008 Sep 11;359(11):1116-27
references: 18784101
references: Oral Oncol. 2013 Mar;49(3):211-5
references: 23079694
references: Cancer. 2001 Dec 1;92(11):2875-84
references: 11753961
references: Nat Genet. 2013 Mar;45(3):253-61
references: 23354438
references: Lancet Oncol. 2011 Apr;12(4):333-43
references: 21377930
references: Nat Genet. 2003 Mar;33(3):416-21
references: 12590261
references: Blood. 2003 Feb 1;101(3):822-6
references: 12393424
references: Cell Mol Life Sci. 2013 Nov;70(21):3989-4008
references: 23307074
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: J Natl Cancer Inst. 2000 May 3;92(9):709-20
references: 10793107
references: Cancer Res. 1996 Jun 1;56(11):2488-92
references: 8653682
references: Nat Rev Cancer. 2009 Oct;9(10):701-13
references: 19693097
references: Radiother Oncol. 2012 Jan;102(1):122-9
references: 21996521
references: Nat Rev Cancer. 2007 Mar;7(3):169-81
references: 17318210
references: N Engl J Med. 2010 Jul 1;363(1):24-35
references: 20530316
references: JAMA. 2012 Feb 15;307(7):693-703
references: 22282321
references: Cancer Discov. 2012 May;2(5):401-4
references: 22588877
references: Clin Cancer Res. 2012 Jan 1;18(1):290-300
references: 22090360
references: Cancer Res. 1993 Oct 1;53(19):4477-80
references: 8402617
references: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4386-91
references: 17671120
references: Nat Genet. 2008 Jun;40(6):707-9
references: 18500343
references: Blood. 2003 Feb 15;101(4):1249-56
references: 12393516
references: Cancer Res. 2007 Apr 1;67(7):3441-9
references: 17409455
references: Cell. 1990 Dec 21;63(6):1129-36
references: 2175676
references: Nat Genet. 2005 Feb;37(2):182-6
references: 15640797
references: Clin Cancer Res. 2011 Nov 15;17(22):7024-34
references: 22068658
references: Eur J Cancer. 2014 Apr;50(6):1100-11
references: 24424107
references: Hum Mutat. 2007 Jun;28(6):622-9
references: 17311302
references: N Engl J Med. 2007 Dec 20;357(25):2552-61
references: 18094376
references: J Oral Pathol Med. 2004 Jul;33(6):317-22
references: 15200478
references: Eur J Cancer. 2010 Jul;46(11):2088-96
references: 20537890
references: Nat Rev Cancer. 2008 Feb;8(2):83-93
references: 18094723
references: Cancer Res. 2010 Jul 1;70(13):5486-96
references: 20530669
references: J Clin Oncol. 2013 Apr 10;31(11):1405-14
references: 23460714
references: Cancer Epidemiol Biomarkers Prev. 1998 Jun;7(6):465-8
references: 9641488
references: Curr Opin Oncol. 2002 May;14(3):310-7
references: 11981277
references: Oncogene. 2008 Sep 18;27(41):5486-96
references: 18794883
references: Radiother Oncol. 2011 Jul;100(1):62-9
references: 21821303
references: Cancer Discov. 2013 Jul;3(7):770-81
references: 23619168
references: Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17761-6
references: 22006338
references: Cancer Treat Rev. 2014 Apr;40(3):390-404
references: 24176789
references: Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a001008
references: 20182602
references: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13568-73
references: 18757741
references: Nat Genet. 1993 May;4(1):42-6
references: 8099841
references: Nature. 2013 Feb 21;494(7437):366-70
references: 23389445
references: Nature. 2014 May 1;509(7498):91-5
references: 24670651
references: Nat Genet. 2013 Oct;45(10):1134-40
references: 24071852
references: Cancer Res. 2003 Mar 15;63(6):1188-91
references: 12649174
references: Cancer Res. 2011 Sep 1;71(17):5923-31
references: 21846821
references: Nat Genet. 2006 Sep;38(9):1043-8
references: 16921376
references: Cancer Res. 1994 Mar 1;54(5):1156-8
references: 8118798
references: Nature. 2013 Oct 17;502(7471):333-339
references: 24132290
references: Nat Rev Cancer. 2011 May;11(5):338-51
references: 21508972
references: Ann Surg Oncol. 2005 Oct;12(10):831-42
references: 16132373
references: Nature. 2013 Aug 22;500(7463):415-21
references: 23945592
references: Clin Cancer Res. 1998 Jul;4(7):1773-8
references: 9676854
references: Future Oncol. 2012 Oct;8(10):1257-71
references: 23130927
references: Cancer Biol Ther. 2010 Oct 1;10(7):689-93
references: 20657180
references: Am J Hum Genet. 2003 Jan;72(1):216-8
references: 12549483
references: J Clin Oncol. 2013 Jan 10;31(2):287-8
references: 23213096
references: J Clin Invest. 2012 Jun;122(6):1951-7
references: 22833868
references: PLoS Genet. 2011 Mar;7(3):e1001333
references: 21437268
references: Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):489-96
references: 19735873
references: Oral Oncol. 2013 Dec;49(12):1121-8
references: 24075955
references: Nat Rev Drug Discov. 2014 Feb;13(2):140-56
references: 24481312
references: Nat Commun. 2013;4:2513
references: 24085110
references: Semin Oncol. 2004 Dec;31(6):726-33
references: 15599850
references: J Virol. 2004 Nov;78(21):11451-60
references: 15479788
references: Nat Rev Cancer. 2011 Jul 07;11(8):558-72
references: 21734724
references: Cancer Epidemiol Biomarkers Prev. 2013 Jun;22(6):1133-41
references: 23629518
references: Cancer Res. 1988 Jun 1;48(11):3282-7
references: 3365707
references: Int J Hematol. 2012 Oct;96(4):413-27
references: 23015417
references: Cancer Res. 1992 Nov 1;52(21):5997-6000
references: 1394225
references: Clin Cancer Res. 2010 Jul 15;16(14):3743-53
references: 20534738
references: Cancer Res. 2013 Oct 15;73(20):6289-98
references: 23980093
references: N Engl J Med. 2006 Feb 9;354(6):567-78
references: 16467544
references: Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):541-50
references: 19190158
references: Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6021-6
references: 23530248
references: Head Neck. 2015 May;37(5):727-34
references: 24596130
references: Am J Clin Oncol. 2016 Feb;39(1):27-31
references: 24401670
references: J Natl Cancer Inst. 1996 Nov 6;88(21):1580-6
references: 8901856