Abstract
Epigenetics refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. Research has shown that epigenetic mechanisms provide an “extra” layer of transcriptional control that regulates how genes are expressed. These mechanisms are critical components in the normal development and growth of cells. Epigenetic abnormalities have been found to be causative factors in cancer, genetic disorders, and pediatric syndromes. Head and neck cancers are a group of malignancies with diverse biological behaviors and a strong, well-established association with environmental effects. Although the hunt for genetic alterations in head and neck cancer has continued in the past two decades, with unequivocal proof of a genetic role in multistage head and neck carcinogenesis, epigenetic alteration in association with promoter CpG islands hypermethylation has emerged in the past few years as one of the most active areas of cancer research. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation is a frequent mechanism in head and neck cancer and achieves increasing diagnostic and therapeutic importance. In this context it is important for clinicians to understand the principles of epigenetic mechanisms and how these principles relate to human health and disease. It is important to address the use of epigenetic pathways in new approaches to molecular diagnosis and novel targeted treatments across the clinical spectrum.
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References
Azad N, Zahnow CA, Rudin CM, Baylin SB (2013) The future of epigenetic therapy in solid tumours–lessons from the past. Nat Rev Clin Oncol 10:256–266
Easwaran H, Baylin SB (2013) Epigenetic abnormalities in cancer find a “home on the range”. Cancer Cell 23:1–3
Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153
Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6:107–116
Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428
Xinarianos G, McRonald FE, Risk JM, Bowers NL, Nikolaidis G, Field JK, Liloglou T (2006) Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer. Hum Mol Genet 15:2038–2044
Clark SJ (2007) Action at a distance: epigenetic silencing of large chromosomal regions in carcinogenesis. Hum Mol Genet 16 Spec No: R88–R95
Nie Y, Yang G, Song Y, Zhao X, So C, Liao J, Wang LD, Yang CS (2001) DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas. Carcinogenesis 22:1615–1623
Matsuzaki K, Deng G, Tanaka H, Kakar S, Miura S, Kim YS (2005) The relationship between global methylation level, loss of heterozygosity, and microsatellite instability in sporadic colorectal cancer. Clin Cancer Res 11:8564–8569
Frigola J, Song J, Stirzaker C, Hinshelwood RA, Peinado MA, Clark SJ (2006) Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nat Genet 38:540–549
Feltus FA, Lee EK, Costello JF, Plass C, Vertino PM (2006) DNA motifs associated with aberrant CpG island methylation. Genomics 87:572–579
Herr P, Hausmann G, Basler K (2012) WNT secretion and signalling in human disease. Trends Mol Med 18:483–493
Bert SA, Robinson MD, Strbenac D, Statham AL, Song JZ, Hulf T, Sutherland RL, Coolen MW, Stirzaker C, Clark SJ (2013) Regional activation of the cancer genome by long-range epigenetic remodeling. Cancer Cell 23:9–22
Tsumagari K, Qi L, Jackson K, Shao C, Lacey M, Sowden J, Tawil R, Vedanarayanan V, Ehrlich M (2008) Epigenetics of a tandem DNA repeat: chromatin DNaseI sensitivity and opposite methylation changes in cancers. Nucleic Acids Res 36:2196–2207
Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet 371:1695–1709
Stewart BW, Greim H, Shuker D, Kauppinen T (2003) Defence of IARC monographs. Lancet 361:1300
Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, Bernstein L, Schoenberg JB, Stemhagen A, Fraumeni JF (1988) Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48:3282–3287
Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269
Sadikovic B, Yoshimoto M, Chilton-MacNeill S, Thorner P, Squire JA, Zielenska M (2009) Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling. Hum Mol Genet 18:1962–1975
Knudson AG (1997) Hereditary predisposition to cancer. Ann N Y Acad Sci 833:58–67
Herman JG, Baylin SB (2000) Promoter-region hypermethylation and gene silencing in human cancer. Curr Top Microbiol Immunol 249:35–54
Suzuki M, Shinohara F, Nishimura K, Echigo S, Rikiishi H (2007) Epigenetic regulation of chemosensitivity to 5-fluorouracil and cisplatin by zebularine in oral squamous cell carcinoma. Int J Oncol 31:1449–1456
Esteller M (2002) CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 21:5427–5440
Weisenberger DJ, Campan M, Long TI, Kim M, Woods C, Fiala E, Ehrlich M, Laird PW (2005) Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res 33:6823–6836
Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Laird PW (2000) MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res 28:E32
Zeschnigk M, Böhringer S, Price EA, Onadim Z, Masshöfer L, Lohmann DR (2004) A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus. Nucleic Acids Res 32:e125
Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A 89:1827–1831
Waterland RA, Lin J-R, Smith CA, Jirtle RL (2006) Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 15:705–716
Xiong Z, Laird PW (1997) COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res 25:2532–2534
Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den Boom D (2005) Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci U S A 102:15785–15790
Costello JF, Smiraglia DJ, Plass C (2002) Restriction landmark genome scanning. Methods 27:144–149
Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schübeler D (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37:853–862
Rauch T, Li H, Wu X, Pfeifer GP (2006) MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells. Cancer Res 66:7939–7947
Califano J, Westra WH, Meininger G, Corio R, Koch WM, Sidransky D (2000) Genetic progression and clonal relationship of recurrent premalignant head and neck lesions. Clin Cancer Res 6:347–352
Bock C (2009) Epigenetic biomarker development. Epigenomics 1:99–110
Relton CL, Davey Smith G (2010) Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment. PLoS Med 7:e1000356
Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 14 Spec No: R47–R58
Beaudet AL (2004) Complex imprinting. Nat Genet 36:793–795
Mann MRW, Chung YG, Nolen LD, Verona RI, Latham KE, Bartolomei MS (2003) Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos. Biol Reprod 69:902–914
Alberio R, Campbell KHS (2003) Epigenetics and nuclear transfer. Lancet 361:1239–1240
Laird PW (2005) Cancer epigenetics. Hum Mol Genet 14 Spec No: R65–R76
Esteller M (2005) DNA methylation and cancer therapy: new developments and expectations. Curr Opin Oncol 17:55–60
Piekarz RL, Bates SE (2009) Epigenetic modifiers: basic understanding and clinical development. Clin Cancer Res 15:3918–3926
Jones PA, Martienssen R (2005) A blueprint for a Human Epigenome Project: the AACR Human Epigenome Workshop. Cancer Res 65:11241–11246
Lund AH, van Lohuizen M (2004) Epigenetics and cancer. Genes Dev 18:2315–2335
Abbott A (2010) Project set to map marks on genome. Nature 463:596–597
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Bakhtiar, S.M., Ali, A., Barh, D. (2015). Epigenetics in Head and Neck Cancer. In: Verma, M. (eds) Cancer Epigenetics. Methods in Molecular Biology, vol 1238. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1804-1_39
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DOI: https://doi.org/10.1007/978-1-4939-1804-1_39
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