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Head and Neck Cancer pp 115–132Cite as

Genetics and Epigenetics of Head and Neck Cancer

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Abstract

Our ability to explore the cancer genome is dependent upon, and limited by, the availability of representative tumour models, the high-quality tissue resource and the capacity of available technologies. Fortunately, there has been great progress in these areas in recent years with next-generation sequencing techniques enabling entire genome sequencing, using a fraction of the resources previously required. Carcinogenesis a multistep and multifactorial process that involves multiple genes with critical events occurring at the DNA level and DNA is a highly stable macromolecule and therefore an excellent resource for biomarker discovery. However, translational perspectives of genomics remain limited which is partly related to intratumour heterogeneity, in which subclones of cells can be present within the same tumour. New advances in therapy will rely upon a greater understanding of the molecular basis of this heterogeneity, and new therapies will have to target the specific characteristics of an individual’s tumour, central to the modern concept of personalised medicine. There is however an emerging molecular classification of HNSCC, with prognostic significance, that is based upon the presence of human papillomavirus and the number of genomic alterations present.

In the last decade, interest has also grown in the epigenetics of cancer. The role of promoter hypermethylation has become a focus for research in many tumour sites, including HNSCC. Silencing of certain TSGs may occur in the absence of genetic change, via aberrant methylation of CpG islands. Several promising avenues exist in attempting to translate this research field into the clinical management of HNSCC. Several suggestions have been made that promoter methylation of specific genes may indicate a particular tumour’s sensitivity to a drug. Epigenetic alterations are particularly interesting since they can potentially be reversed in drug treatment with mechanisms such as epigenetic reprogramming suggested. This opens the door for using epigenetic modifiers as therapeutic agents.

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References

  1. Stransky N, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Agrawal N, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (I). Oral Oncol. 2010;46(9):630–5.

    Article  PubMed  Google Scholar 

  4. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11(1):9–22.

    Article  CAS  PubMed  Google Scholar 

  5. Pickering CR, et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov. 2013;3(7):770–81.

    Article  CAS  PubMed  Google Scholar 

  6. Smeets SJ, et al. Genetic classification of oral and oropharyngeal carcinomas identifies subgroups with a different prognosis. Cell Oncol. 2009;31(4):291–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Walter V, et al. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes. PLoS One. 2013;8(2), e56823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mroz EA, Rocco JW. MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma. Oral Oncol. 2013;49(3):211–5.

    Article  CAS  PubMed  Google Scholar 

  9. Boveri T. Zur Frage der Entstehlung MalignerTumoren. Jena, Germany: Gustave Fischer; 1914.

    Google Scholar 

  10. Barrett JC. Mechanisms of multistep carcinogenesis and carcinogen risk assessment. Environ Health Perspect. 1993;100:9–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953;6(5):963–8.

    Article  CAS  PubMed  Google Scholar 

  12. Braakhuis BJ, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63(8):1727–30.

    CAS  PubMed  Google Scholar 

  13. Graveland AP, et al. Loss of heterozygosity at 9p and p53 immunopositivity in surgical margins predict local relapse in head and neck squamous cell carcinoma. Int J Cancer. 2011;128(8):1852–9.

    Article  CAS  PubMed  Google Scholar 

  14. Alitalo K, Schwab M. Oncogene amplification in tumor cells. Adv Cancer Res. 1986;47:235–81.

    Article  CAS  PubMed  Google Scholar 

  15. Haluska FG, Tsujimoto Y, Croce CM. Oncogene activation by chromosome translocation in human malignancy. Annu Rev Genet. 1987;21:321–45.

    Article  CAS  PubMed  Google Scholar 

  16. Klein G, Klein E. Evolution of tumours and the impact of molecular oncology. Nature. 1985;315(6016):190–5.

    Article  CAS  PubMed  Google Scholar 

  17. Field JK. The role of oncogenes and tumour-suppressor genes in the aetiology of oral, head and neck squamous cell carcinoma. J R Soc Med. 1995;88(1):35P–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Sidransky D. Molecular genetics of head and neck cancer. Curr Opin Oncol. 1995;7(3):229–33.

    Article  CAS  PubMed  Google Scholar 

  19. Ishitoya J, et al. Gene amplification and overexpression of EGF receptor in squamous cell carcinomas of the head and neck. Br J Cancer. 1989;59(4):559–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang SS, Califano J. Current status of biomarkers in head and neck cancer. J Surg Oncol. 2008;97(8):640–3.

    Article  PubMed  Google Scholar 

  21. Bonner JA, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.

    Article  CAS  PubMed  Google Scholar 

  22. Eberhard DA, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;23(25):5900–9.

    Article  CAS  PubMed  Google Scholar 

  23. Patturajan M, et al. DeltaNp63 induces beta-catenin nuclear accumulation and signaling. Cancer Cell. 2002;1(4):369–79.

    Article  CAS  PubMed  Google Scholar 

  24. Rosenthal EL, Matrisian LM. Matrix metalloproteases in head and neck cancer. Head Neck. 2006;28(7):639–48.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Molinolo AA, et al. Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative. Clin Cancer Res. 2007;13(17):4964–73.

    Article  CAS  PubMed  Google Scholar 

  26. Kandoth C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Holsinger FC, et al. Biomarker-directed therapy of squamous carcinomas of the head and neck: targeting PI3K/PTEN/mTOR pathway. J Clin Oncol. 2013;31(9):e137–40.

    Article  PubMed  Google Scholar 

  28. India Project Team of the International Cancer Genome, C. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013;4:2873.

    Google Scholar 

  29. Bos JL. ras Oncogenes in human cancer: a review. Cancer Res. 1989;49(17):4682–9.

    CAS  PubMed  Google Scholar 

  30. Smeets SJ, et al. Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus. Oncogene. 2006;25(17):2558–64.

    Article  CAS  PubMed  Google Scholar 

  31. Aaronson DS, Horvath CM. A road map for those who don’t know JAK-STAT. Science. 2002;296(5573):1653–5.

    Article  CAS  PubMed  Google Scholar 

  32. Weinberg RA. Tumor suppressor genes. Science (New York, NY). 1991;254(5035):1138–46.

    Article  CAS  Google Scholar 

  33. Choi S, Myers JN. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 2008;87(1):14–32.

    Article  CAS  PubMed  Google Scholar 

  34. Knudson AG. Genetics and etiology of human cancer. Adv Hum Genet. 1977;8:1–66.

    CAS  PubMed  Google Scholar 

  35. Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet. 1993;9(4):138–41.

    Article  CAS  PubMed  Google Scholar 

  36. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88(3):323–31.

    Article  CAS  PubMed  Google Scholar 

  37. Bradford CR, et al. P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines. Head Neck. 2003;25(8):654–61.

    Article  PubMed  Google Scholar 

  38. Poeta ML, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007;357(25):2552–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Temam S, et al. p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2000;18(2):385–94.

    CAS  PubMed  Google Scholar 

  40. Carvalho AL, et al. Deleted in colorectal cancer is a putative conditional tumor-suppressor gene inactivated by promoter hypermethylation in head and neck squamous cell carcinoma. Cancer Res. 2006;66(19):9401–7.

    Article  CAS  PubMed  Google Scholar 

  41. Nakaya K, et al. Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array. Oncogene. 2007;26(36):5300–8.

    Article  CAS  PubMed  Google Scholar 

  42. Califano J, et al. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res. 1996;56(11):2488–92.

    CAS  PubMed  Google Scholar 

  43. van der Riet P, et al. Frequent loss of chromosome 9p21-22 early in head and neck cancer progression. Cancer Res. 1994;54(5):1156–8.

    PubMed  Google Scholar 

  44. Perez-Sayans M, et al. p16(INK4a)/CDKN2 expression and its relationship with oral squamous cell carcinoma is our current knowledge enough? Cancer Lett. 2011;306(2):134–41.

    Article  CAS  PubMed  Google Scholar 

  45. Lukas J, et al. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature. 1995;375(6531):503–6.

    Article  CAS  PubMed  Google Scholar 

  46. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366(6456):704–7.

    Article  CAS  PubMed  Google Scholar 

  47. Serrano M, et al. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science (New York, NY). 1995;267(5195):249–52.

    Article  CAS  Google Scholar 

  48. Goodger NM, et al. Cell cycle regulatory proteins–an overview with relevance to oral cancer. Oral Oncol. 1997;33(2):61–73.

    Article  CAS  PubMed  Google Scholar 

  49. Riaz N, et al. Unraveling the molecular genetics of head and neck cancer through genome-wide approaches. Genes Dis. 2014;1(1):75–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Garnis C, et al. Use of complete coverage array comparative genomic hybridization to define copy number alterations on chromosome 3p in oral squamous cell carcinomas. Cancer Res. 2003;63(24):8582–5.

    CAS  PubMed  Google Scholar 

  51. Mao L, et al. Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment. Nat Med. 1996;2(6):682–5.

    Article  CAS  PubMed  Google Scholar 

  52. Dong SM, et al. Epigenetic inactivation of RASSF1A in head and neck cancer. Clin Cancer Res. 2003;9(10 Pt 1):3635–40.

    CAS  PubMed  Google Scholar 

  53. Carr AM. Cell cycle. Piecing together the p53 puzzle. Science. 2000;287(5459):1765–6.

    Article  CAS  PubMed  Google Scholar 

  54. Buschmann T, et al. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell. 2000;101(7):753–62.

    Article  CAS  PubMed  Google Scholar 

  55. Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003;1(14):1001–8.

    CAS  PubMed  Google Scholar 

  56. Zhou G, et al. Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation. Mol Cell. 2014;54(6):960–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Berenson JR, Yang J, Mickel RA. Frequent amplification of the bcl-1 locus in head and neck squamous cell carcinomas. Oncogene. 1989;4(9):1111–6.

    CAS  PubMed  Google Scholar 

  58. Callender T, et al. PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer. 1994;74(1):152–8.

    Article  CAS  PubMed  Google Scholar 

  59. Cheng KC, Loeb LA. Genomic instability and tumor progression: mechanistic considerations. Adv Cancer Res. 1993;60:121–56.

    Article  CAS  PubMed  Google Scholar 

  60. Fanconi G. Familiäre infantile perniziosaartige Anämie (perniziöses Blutbild und Konstitution). Jahrbuch für Kinderheilkunde und physische Erziehung (Wien). 1927;117:257–80.

    Google Scholar 

  61. Lustig JP, et al. Head and neck carcinoma in Fanconi’s anaemia–report of a case and review of the literature. Eur J Cancer Part B Oral Oncol. 1995;31B(1):68–72.

    Article  CAS  Google Scholar 

  62. Kaplan MJ, et al. Squamous cell carcinoma in the immunosuppressed patient: Fanconi’s anemia. Laryngoscope. 1985;95(7 Pt 1):771–5.

    CAS  PubMed  Google Scholar 

  63. Sparano A, et al. Genome-wide profiling of oral squamous cell carcinoma by array-based comparative genomic hybridization. Laryngoscope. 2006;116(5):735–41.

    Article  CAS  PubMed  Google Scholar 

  64. Wang Y, et al. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 2000;14(8):927–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Meetei AR, et al. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol Cell Biol. 2003;23(10):3417–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Garkavtsev IV, et al. The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control. Oncogene. 2001;20(57):8276–80.

    Article  CAS  PubMed  Google Scholar 

  67. Gatti RA, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature. 1988;336(6199):577–80.

    Article  CAS  PubMed  Google Scholar 

  68. Lazar AD, et al. Loss of heterozygosity at 11q23 in squamous cell carcinoma of the head and neck is associated with recurrent disease. Clin Cancer Res. 1998;4(11):2787–93.

    CAS  PubMed  Google Scholar 

  69. Savitsky K, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science (New York, NY). 1995;268(5218):1749–53.

    Article  CAS  Google Scholar 

  70. Ai L, et al. Ataxia-telangiectasia-mutated (ATM) gene in head and neck squamous cell carcinoma: promoter hypermethylation with clinical correlation in 100 cases. Cancer Epidemiol Biomarkers Prev. 2004;13(1):150–6.

    Article  CAS  PubMed  Google Scholar 

  71. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003;3(3):155–68.

    Article  CAS  PubMed  Google Scholar 

  72. Bootsma D, Kraemer KH, Cleaver JE, Hoeijmakers JHJ. Nucleotide excision repair syndromes: Xeroderma pigmentosum, Cockayne syndrome, and trichoth iodystophy. In: Vogelstein B, Kinzler KW, editors. The genetic basis of human cancer. 2nd ed. New York: McGraw Hill; 2002. p. 211–37.

    Google Scholar 

  73. Cleaver JE. Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nat Rev Cancer. 2005;5(7):564–73.

    Article  CAS  PubMed  Google Scholar 

  74. Santibanez-Koref MF, et al. p53 germline mutations in Li-Fraumeni syndrome. Lancet. 1991;338(8781):1490–1.

    Article  CAS  PubMed  Google Scholar 

  75. Akashi M, Koeffler HP. Li-Fraumeni syndrome and the role of the p53 tumor suppressor gene in cancer susceptibility. Clin Obstet Gynecol. 1998;41(1):172–99.

    Article  CAS  PubMed  Google Scholar 

  76. Trizna Z, Schantz SP. Hereditary and environmental factors associated with risk and progression of head and neck cancer. Otolaryngol Clin North Am. 1992;25(5):1089–103.

    CAS  PubMed  Google Scholar 

  77. Fishel R, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75(5):1027–38.

    Article  CAS  PubMed  Google Scholar 

  78. Hsu TC, et al. Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis. Int J Cancer. 1989;43(3):403–9.

    Article  CAS  PubMed  Google Scholar 

  79. Field JK. Genomic instability in squamous cell carcinoma of the head and neck. Anticancer Res. 1996;16(4C):2421–31.

    CAS  PubMed  Google Scholar 

  80. Schantz SP, et al. Genetic susceptibility to head and neck cancer: interaction between nutrition and mutagen sensitivity. Laryngoscope. 1997;107(6):765–81.

    Article  CAS  PubMed  Google Scholar 

  81. Foulkes WD, et al. Familial risks of squamous cell carcinoma of the head and neck: retrospective case-control study. BMJ (Clin Res Ed). 1996;313(7059):716–21.

    Article  CAS  PubMed Central  Google Scholar 

  82. Zhuo W, et al. CYP1A1 and GSTM1 polymorphisms and oral cancer risk: association studies via evidence-based meta-analyses. Cancer Invest. 2009;27(1):86–95.

    Article  CAS  PubMed  Google Scholar 

  83. Sato M, et al. Genetically high susceptibility to oral squamous cell carcinoma in terms of combined genotyping of CYP1A1 and GSTM1 genes. Oral Oncol. 2000;36(3):267–71.

    Article  CAS  PubMed  Google Scholar 

  84. Tanimoto K, et al. Polymorphisms of the CYP1A1 and GSTM1 gene involved in oral squamous cell carcinoma in association with a cigarette dose. Oral Oncol. 1999;35(2):191–6.

    Article  CAS  PubMed  Google Scholar 

  85. Anantharaman D, et al. Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis. 2007;28(7):1455–62.

    Article  CAS  PubMed  Google Scholar 

  86. Ha PK, et al. Molecular techniques and genetic alterations in head and neck cancer. Oral Oncol. 2009;45(4–5):335–9.

    Article  CAS  PubMed  Google Scholar 

  87. Uchida K, et al. Molecular cytogenetic analysis of oral squamous cell carcinomas by comparative genomic hybridization, spectral karyotyping, and fluorescence in situ hybridization. Cancer Genet Cytogenet. 2006;167(2):109–16.

    Article  CAS  PubMed  Google Scholar 

  88. Latif F, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science (New York, NY). 1993;260(5112):1317–20.

    Article  CAS  Google Scholar 

  89. Kinzler KW, et al. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science (New York, NY). 1991;251(4999):1366–70.

    Article  CAS  Google Scholar 

  90. Williams ME, et al. Chromosome 11Q13 amplification in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1993;119(11):1238–43.

    Article  CAS  PubMed  Google Scholar 

  91. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975;98(3):503–17.

    Article  CAS  PubMed  Google Scholar 

  92. Southern E, Mir K, Shchepinov M. Molecular interactions on microarrays. Nat Genet. 1999;21(1 Suppl):5–9.

    Article  CAS  PubMed  Google Scholar 

  93. Mendez E, et al. A genetic expression profile associated with oral cancer identifies a group of patients at high risk of poor survival. Clin Cancer Res. 2009;15(4):1353–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Chung CH, et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell. 2004;5(5):489–500.

    Article  CAS  PubMed  Google Scholar 

  95. Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94(3):441–8.

    Article  CAS  PubMed  Google Scholar 

  96. Okano M, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99(3):247–57.

    Article  CAS  PubMed  Google Scholar 

  97. Paroush Z, et al. Dynamics of demethylation and activation of the alpha-actin gene in myoblasts. Cell. 1990;63(6):1229–37.

    Article  CAS  PubMed  Google Scholar 

  98. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008;9(6):465–76.

    Article  CAS  PubMed  Google Scholar 

  99. Shivaswamy S, et al. Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biol. 2008;6(3), e65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Fatemi M, et al. Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level. Nucleic Acids Res. 2005;33(20), e176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Schuebel KE, et al. Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS Genet. 2007;3(9):1709–23.

    Article  CAS  PubMed  Google Scholar 

  102. Sjoblom T, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314(5797):268–74.

    Article  PubMed  CAS  Google Scholar 

  103. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983;301(5895):89–92.

    Article  CAS  PubMed  Google Scholar 

  104. Sakai T, et al. Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet. 1991;48(5):880–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128(4):683–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Baylin SB, Ohm JE. Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 2006;6(2):107–16.

    Article  CAS  PubMed  Google Scholar 

  107. Schlesinger Y, et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet. 2007;39(2):232–6.

    Article  CAS  PubMed  Google Scholar 

  108. Tiwari VK, et al. PcG proteins, DNA methylation, and gene repression by chromatin looping. PLoS Biol. 2008;6(12):2911–27.

    Article  CAS  PubMed  Google Scholar 

  109. Schepers A, Clevers H. Wnt signaling, stem cells, and cancer of the gastrointestinal tract. Cold Spring Harb Perspect Biol. 2012;4(4):a007989.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell. 2012;22(1):9–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Barretina J, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483(7391):603–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Poage GM, et al. Global hypomethylation identifies Loci targeted for hypermethylation in head and neck cancer. Clin Cancer Res. 2011;17(11):3579–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ha PK, Califano JA. Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma. Lancet Oncol. 2006;7(1):77–82.

    Article  CAS  PubMed  Google Scholar 

  114. Shaw R. The epigenetics of oral cancer. Int J Oral Maxillofac Surg. 2006;35(2):101–8.

    Article  CAS  PubMed  Google Scholar 

  115. Herman JG, et al. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A. 1996;93(18):9821–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Easds CA, Danenberg KD, Kawakami K. Methylight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 2000;28(SRC – GoogleScholar):E32.

    Google Scholar 

  117. Colella S, et al. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques. 2003;35(1):146–50.

    CAS  PubMed  Google Scholar 

  118. Shaw RJ, et al. Promoter methylation of P16, RAcadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing. Br J Cancer. 2006;94:561–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Shaw RJ, et al. The role of pyrosequencing in head and neck cancer epigenetics: correlation of quantitative methylation data with gene expression. Arch Otolaryngol Head Neck Surg. 2008;134(3):251–6.

    Article  PubMed  Google Scholar 

  120. Bibikova M, et al. High-throughput DNA methylation profiling using universal bead arrays. Genome Res. 2006;16(3):383–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Hoque MO, et al. Genome-wide promoter analysis uncovers portions of the cancer methylome. Cancer Res. 2008;68(8):2661–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Tokumaru Y, et al. Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res. 2004;64(17):5982–7.

    Article  CAS  PubMed  Google Scholar 

  123. Jithesh PV, et al. The epigenetic landscape of oral squamous cell carcinoma. Br J Cancer. 2013;108(2):370–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Fouse SD, Nagarajan RO, Costello JF. Genome-scale DNA methylation analysis. Epigenomics. 2010;2(1):105–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. El-Naggar AK, et al. Methylation, a major mechanism of p16/CDKN2 gene inactivation in head and neck squamous carcinoma. Am J Pathol. 1997;151(6 SRC – GoogleScholar):1767–74.

    Google Scholar 

  126. Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96(15):8681–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. van Kempen PM, et al. Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: a systematic review. Epigenetics. 2014;9(2):194–203.

    Article  PubMed  CAS  Google Scholar 

  128. Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003;3(4):253–66.

    Article  CAS  PubMed  Google Scholar 

  129. Matthews AM, et al. Saliva collection methods for DNA biomarker analysis in oral cancer patients. Br J Oral Maxillofac Surg. 2013;51(5):394–8.

    Article  PubMed  Google Scholar 

  130. Shaw RJ, et al. Methylation enrichment pyrosequencing: combining the specificity of MSP with validation by pyrosequencing. Nucleic Acids Res. 2006;34(11), e78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Righini CA, et al. Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence. Clin Cancer Res. 2007;13(4):1179–85.

    Article  CAS  PubMed  Google Scholar 

  132. Carvalho AL, et al. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clin Cancer Res. 2008;14(1):97–107.

    Article  CAS  PubMed  Google Scholar 

  133. Goldenberg D, et al. Intraoperative molecular margin analysis in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(1 SRC – GoogleScholar):39–44.

    Google Scholar 

  134. Shaw RJ, et al. Quantitative methylation analysis of resection margins and lymph nodes in oral squamous cell carcinoma. Br Maxillofac Surg. 2007;45(8 SRC – GoogleScholar):617–22.

    Google Scholar 

  135. Tan HK, et al. Quantitative methylation analyses of resection margins predict local recurrences and disease-specific deaths in patients with head and neck squamous cell carcinomas. Br J Cancer. 2008;99(2):357–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Hayashi M, et al. Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma. Cancer. 2015;121(12):1957–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Shaw RJ, et al. Molecular staging of surgical margins in oral squamous cell carcinoma using promoter methylation of p16(INK4A), cytoglobin, E-cadherin, and TMEFF2. Ann Surg Oncol. 2013;20(8):2796–802.

    Article  PubMed  Google Scholar 

  138. Shaw RJ, et al. Extracapsular spread in oral squamous cell carcinoma. Head Neck. 2010;32(6):714–22.

    PubMed  Google Scholar 

  139. Lopez M, et al. Gene promoter hypermethylation in oral rinses of leukoplakia patients–a diagnostic and/or prognostic tool? Eur J Cancer. 2003;39(16 SRC – GoogleScholar):2306–9.

    Google Scholar 

  140. Hall GL, et al. p16 Promoter methylation is a potential predictor of malignant transformation in oral epithelial dysplasia. Cancer Epidemiol Biomarkers Prev. 2008;17(8):2174–9.

    Article  CAS  PubMed  Google Scholar 

  141. Shi H, et al. Association between P16INK4a promoter methylation and HNSCC: a meta-analysis of 21 published studies. PLoS One. 2015;10(4), e0122302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Esteller M, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343(19):1350–4.

    Article  CAS  PubMed  Google Scholar 

  143. Banno K, et al. Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. Int J Oncol. 2007;31(4):713–20.

    CAS  PubMed  Google Scholar 

  144. Steele N, et al. Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo. Br J Cancer. 2009;100(5):758–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Kang H, et al. Long-term use of valproic acid in US veterans is associated with a reduced risk of smoking-related cases of head and neck cancer. Cancer. 2014;120(9):1394–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Queen Victoria Hospital, East Grinstead, West Sussex, UK

    Jagtar Dhanda BSc(Hons) MFDSRCS,FRCS(OMFS),PhD

  2. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK

    Richard J. Shaw MD, FDS, FRCS(OMFS)

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  1. Jagtar Dhanda BSc(Hons) MFDSRCS,FRCS(OMFS),PhD
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  2. Richard J. Shaw MD, FDS, FRCS(OMFS)
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Correspondence to Jagtar Dhanda BSc(Hons) MFDSRCS,FRCS(OMFS),PhD .

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  1. Department of Radio-Oncology, Genolier Swiss Medical Network, Genolier, Switzerland

    Jacques Bernier

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Dhanda, J., Shaw, R.J. (2016). Genetics and Epigenetics of Head and Neck Cancer. In: Bernier, J. (eds) Head and Neck Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-27601-4_5

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