Abstract
Unlike genetic regulation, the epigenetic regulation of gene expression does not involve mutations, but involves promoter methylation and histone deacetylation. It is challenging to define how promoter hypermethylation participates in gene silencing and how the loss of methylation alters chromosome structure. Nevertheless, the findings of DNA methylation abnormalities in cancer have a potential clinical impact. One of the potential targets appears to lie in the use of CpG hypermethylation events as tumor biomarkers. The promoter changes provide a positive signal for cancer cells that can be detected by conventional techniques. Based on recent research, it seems reasonable to use multiple markers for predicting one tumor type. As almost every tumor type appears to have multiple independent promoter hypermethylation events, a panel of markers might be constructed to provide indices for monitoring cancer risk assessment and early cancer detection. Because epigenetic events are reversible, chemical agents can be used to intervene epigenetic events.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet 1996; 30:441–464.
Santini V, Kantarjian HM, Issa JP. Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann Intern Med 2001; 134:573–586.
Esteller M, Fraga MF, Guo M, et al. DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet 2001; 10:3001–3007.
Esteller M, Herman JG. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 2002; 196:1–7.
Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000; 1:11–19.
Fruhwald MC, Plass C. Global and gene-specific methylation patterns in cancer: aspects of tumor biology and clinical potential. Mol Genet Metab 2002; 75:1–16.
Bird AP. CpG-rich islands and the function of DNA methylation. Nature 1986; 321:209–213.
Baylin SB. Tying it all together: epigenetics, genetics, cell cycle, and cancer. Science 1997; 277: 1948–1949.
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002; 3: 415–428.
Takacs M, Salamon D, Myohanen S, et al. Epigenetics of latent Epstein-Barr virus genomes: high resolution methylation analysis of the bidirectional promoter region of latent membrane protein 1 and 2B genes. Biol Chem 2001; 382:699–705.
Tierney RJ, Kirby HE, Nagra JK, Desmond J, Bell AI, Rickinson AB. Methylation of transcription factor binding sites in the Epstein-Barr virus latent cycle promoter Wp coincides with promoter downregulation during virus-induced B-cell transformation. J Virol 2000; 74:10,468–10,479.
Robertson KD. The role of DNA methylation in modulating Epstein-Barr virus gene expression. Curr Topics Microbiol Immunol 2000; 249:21–34.
Tao Q, Swinnen LJ, Yang J, Srivastava G, Robertson KD, Ambinder RF. Methylation status of the Epstein-Barr virus major latent promoter C in iatrogenic B cell lymphoproliferative disease. Application of PCR-based analysis. Am J Pathol 1999; 155:619–625.
Hagan CR, Rudin CM. Mobile genetic element activation and genotoxic cancer therapy: potential clinical implications. Am J Pharmacogenomics 2002; 2:25–35.
Nelson WG, De Marzo AM, Deweese TL, et al. Preneoplastic prostate lesions: an opportunity for prostate cancer prevention. Ann NY Acad Sci 2001; 952:135–144.
Rideout WM 3rd, Eggan K, Jaenisch R. Nuclear cloning and epigenetic reprogramming of the genome. Science 2001; 293:1093–1098.
Nelson WG, De Marzo AM, DeWeese TL. The molecular pathogenesis of prostate cancer: Implications for prostate cancer prevention. Urology 2001; 57:39–45.
Howell CY, Bestor TH, Ding F, et al. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 2001; 104:829–838.
El-Osta A, Wolffe AP. DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease. Gene Express 2000; 9:63–75.
Zuccotti M, Garagna S, Redi CA. Nuclear transfer, genome reprogramming and novel opportunities in cell therapy. J Endocrinol Invest 2000; 23:623–629.
Feinberg AP. Cancer epigenetics takes center stage. Proc Natl Acad Sci USA 2001; 98:392–394.
Feinberg AP. DNA methylation, genomic imprinting and cancer. Curr Topics Microbiol Immunol 2000; 249:87–99.
Hu L, Troyanovsky B, Zhang X, Trivedi P, Ernberg I, Klein G. Differences in the immunogenicity of latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus genomes derived from LMP1-positive and-negative nasopharyngeal carcinoma. Cancer Res 2000; 60:5589–5593.
Rice JC, Allis CD. Histone methylation versus histone acetylation: new insights into epigenetic regulation. Curr Opin Cell Biol 2001; 13:263–273.
Kruhlak MJ, Hendzel MJ, Fischle W, et al. Regulation of global acetylation in mitosis through loss of histone acetyltransferases and deacetylases from chromatin. J Biol Chem 2001; 276:38,307–38,319.
Surani MA. Genetics: immaculate misconception. Nature 2002; 416:491–493.
Surani MA. Imprinting and the initiation of gene silencing in the germ line. Cell 1998; 93: 309–312.
Costa M, Klein CB. Nickel carcinogenesis, mutation, epigenetics, or selection. Environ Health Perspect 1999; 107:A438–A439.
Breivik J, Gaudernack G. Genomic instability, DNA methylation, and natural selection in colorectal carcinogenesis. Semin Cancer Biol 1999; 9:245–254.
Breivik J, Gaudernack G. Carcinogenesis and natural selection: a new perspective to the genetics and epigenetics of colorectal cancer. Adv Cancer Res 1999; 76:187–212.
Kinzler KW, Vogelstein B. Landscaping the cancer terrain. Science 1998; 280:1036–1037.
Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 2000; 16:168–174.
Esteller M, Catasus L, Matias-Guiu X, et al. hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 1999; 155:1767–1772.
Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 1999; 59:793–797.
Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res 1999; 59:67–70.
Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet 1999; 21:163–167.
Tycko B. Epigenetic gene silencing in cancer. J Clin Invest 2000; 105:401–407.
Akhtar M, Cheng Y, Magno RM, et al. Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res 2001; 61:2399–2403.
Ahluwalia A, Yan P, Hurteau JA, et al. DNA methylation and ovarian cancer. I. Analysis of CpG island hypermethylation in human ovarian cancer using differential methylation hybridization. Gynecol Oncol 2001; 82: 261–268.
Ahluwalia A, Hurteau JA, Bigsby RM, Nephew KP. DNA methylation in ovarian cancer. II. Expression of DNA methyltransferases in ovarian cancer cell lines and normal ovarian epithelial cells. Gynecol Oncol 2001; 82: 299–304.
Ng HH, Zhang Y, Hendrich B, et al. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet 1999; 23:58–61.
Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP. Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 1999; 23:62–66.
Nan BC, Shao DM, Chen HL, et al. Alteration of N-acetylglucosaminyltransferases in pancreatic carcinoma. Glycoconj J 1998; 15:1033–1037.
Barbieri R, Mischiati C, Piva R, et al. DNA methylation of the Ha-ras-1 oncogene in neoplastic cells. Anticancer Res 1989; 9:1787–1791.
Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 1993; 82:1820–1828.
Ray JS, Harbison ML, McClain RM, Goodman JI. Alterations in the methylation status and expression of the raf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse live tumors. Mol Carcinog 1994; 9: 155–166.
Rao PM, Antony A, Rajalakshmi S, Sarma DS. Studies on hypomethylation of liver DNA during early stages of chemical carcinogenesis in rat liver. Carcinogenesis 1989; 10:933–937.
Vachtenheim J, Horakova I, Novotna H. Hypomethylation of CCGG sites in the 3′ region of H-ras protooncogene is frequent and is associated with H-ras allele loss in non-small cell lung cancer. Cancer Res 1994; 54:1145–1148.
Feinberg AP, Vogelstein B. Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Commun 1983; 111:47–54.
Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983; 301:89–92.
Chandler LA, DeClerck YA, Bogenmann E, Jones PA. Patterns of DNA methylation and gene expression in human tumor cell lines. Cancer Res 1986; 46:2944–2949.
Stephenson J, Akdag R, Ozbek N, Mufti GJ. Methylation status within exon 3 of the c-myc gene as a prognostic marker in myeloma and leukaemia. Leuk Res 1993; 17:291–293.
Issa JP. The epigenetics of colorectal cancer. Ann NY Acad Sci 2000; 910:140–153; discussion 153-155.
Yeager TR, DeVries S, Jarrard DF, et al. Overcoming cellular senescence in human cancer pathogenesis. Genes Dev 1998; 12:163–174.
Markowitz S, Wang J, Myeroff L, et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995; 268:1336–1368.
Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998; 58:5248–5257.
Zheng M, Wang H, Zhang H, et al. The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells. J Cancer Res Clin Oncol 1999; 125:357–360.
Eads CA, Danenberg KD, Kawakami K, et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res 2000; 28:E32.
Mintz A, Debinski W. Cancer genetics/epigenetics and the X chromosome: possible new links for malignant glioma pathogenesis and immune-based therapies. Crit Rev Oncog 2000; 11:77–95.
Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 1996; 93:9821–9826.
Wei SH, Chen CM, Strathdee G, et al. Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progression-free survival in patients and identifies candidate epigenetic markers. Clin Cancer Res 2002; 8:2246–2252.
Chen CM, Chen HL, Hsiau TH, et al. Methylation target array for rapid analysis of CpG island hypermethylation in multiple tissue genomes. Am J Pathol 2003; 163:37–45.
Xiong Z, Laird PW. COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res 1997; 25:2532–2534.
Adorjan P, Distler J, Lipscher E, et al. Tumour class prediction and discovery by microarray-based DNA methylation analysis. Nucleic Acids Res 2002; 30:e21.
Hatada I, Kato A, Morita S, et al. A microarray-based method for detecting methylated loci. J Hum Genet 2002; 47:448–451.
Shi H, Yan PS, Chen CM, et al. Expressed CpG island sequence tag microarray for dual screening of DNA hypermethylation and gene silencing in cancer cells. Cancer Res 2002; 62:3214–3220.
Momparler RL, Cote S, Eliopoulos N. Pharmacological approach for optimization of the dose schedule of 5-aza-2′-deoxycytidine (Decitabine) for the therapy of leukemia. Leukemia 1997; 11(Suppl 1): S1–S6.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Verma, M., Srivastava, S. (2005). Implications of Epigenetics for Early Cancer Diagnosis and Prevention. In: LaRochelle, W.J., Shimkets, R.A. (eds) The Oncogenomics Handbook. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-893-5:365
Download citation
DOI: https://doi.org/10.1385/1-59259-893-5:365
Publisher Name: Humana Press
Print ISBN: 978-1-58829-425-8
Online ISBN: 978-1-59259-893-9
eBook Packages: MedicineMedicine (R0)