Advertisement

The Loss of Methyl Groups in DNA of Tumor Cells and Tissues

The Immunochemical Approach
  • Alain Niveleau
  • Chandrika Piyathilake
  • Adriana de Capoa
  • Claudio Grappelli
  • Jean-Marc Dumollard
  • Lucien Frappart
  • Emmanuel Drouet
Chapter
  • 911 Downloads
Part of the Medical Intelligence Unit book series (MIUN)

Abstract

The existence of 5-methyldeoxycytidine (5-MeCyd) has been first demonstrated in 1958. For several years the presence of this naturally modified base in DNA remained unexplained and its role was ignored until a relationship was established between the expression of ovalbumin and the methylation status of the gene coding for this protein in various tissues. The gene was not methylated in the oviduct whereas it was methylated in the brain where ovalbumin was not expressed. This first observation prompted numerous studies that investigated the distribution and the role of this modified base in genomic DNA. A further significant progress was accomplished when it was demonstrated that tumor genomes were globally less methylated than their normal counterparts. This important observation was made using DNA that had been extracted from tissue samples and then submitted to extensive digestion by nucleases and reverse phase high pressure liquid chromatography analysis. The development of gene-specific hybridization techniques together with the availability of an ever-increasing number of methylation-sensitive restriction enzymes allowed the methylation status of numerous genes to be investigated, especially DNA derived from tumors. This gene-specific analysis has revealed that in addition to genome-wide hypomethylation, local hypermethylated sites were identified in tumors in concert with an increased DNA methyltransferase activity. For several years most studies in the field-aimed at the detection of altered methylation patterns of oncogenes ^ or tumor suppressor genes.

Keywords

Squamous Cell Carcinoma Methylation Status Epithelial Hyperplasia Global Hypomethylation Normal Bronchial Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hotchkiss RD. The quantitative separation of purines, pyrimidines and nucleosides by paper chromatography. J Biol Chem 1948; 175:315–332.Google Scholar
  2. 2.
    Mandel JL, Chambon P. DNA methylation: Organ specific variations in tne methylation pattern within and around ovalbumin and other chicken genes. Nucleic Acids Res 1979; 20:2081–2103.CrossRefGoogle Scholar
  3. 3.
    Razin A, Riggs AD. DNA methylation and gene function. Science 1980; 210:604–610.PubMedCrossRefGoogle Scholar
  4. 4.
    Ehrlich M, Wang RY. 5-Methylcytosine in eukaryotic DNA. Science 1981; 212:1350–1357.PubMedCrossRefGoogle Scholar
  5. 5.
    Ehrlich M, Gama-Sosa MA, Huang L et al. Amount and distribution of 5-methyl-cytosine in human DNA from different type of tissues or cells. Nucl Acids Res 1982; 10:2709–2721.PubMedCrossRefGoogle Scholar
  6. 6.
    Bird A. CpG-rich islands and fuction of DNA methylation. Nature 1986; 321:209–213.PubMedCrossRefGoogle Scholar
  7. 7.
    Hsieh CL. Dependence of transcriptional repression on CpG methylation density. Mol Cell Biol 1994; 14:5487–5494.PubMedGoogle Scholar
  8. 8.
    Muiznieks I, Doerfler W. The impact of 5′-CG-3′ methylation on the activity of different eukaryotic promoters: A comparative study. FEBS Lett 1994; 344:251–254.PubMedCrossRefGoogle Scholar
  9. 9.
    Lapeyre JN, Becker FF. 5-methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem Biophys Res Commun 1979; 87:698–705.PubMedCrossRefGoogle Scholar
  10. 10.
    Gama-Sosa MA, Slagel VA, Trewyn RW et al. The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res 1983; 11:6883–6894.PubMedCrossRefGoogle Scholar
  11. 11.
    Diala ES, Cheah MS, Rowitch D et al. Extent of DNA methylation in human tumor cells. J Natl Cancer Inst 1983; 71:755–764.PubMedGoogle Scholar
  12. 12.
    Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983; 301:89–92.PubMedCrossRefGoogle Scholar
  13. 13.
    Goelz SE, Vogelstein B, Hamilton SR et al. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 1985; 228:187–190.PubMedCrossRefGoogle Scholar
  14. 14.
    Feinberg AP, Gehrke CW, Kuo KC et al. Reduced genomic 5-methylcytosine in human colonic neoplasia. Cancer Res 1988; 48:1159–1161.PubMedGoogle Scholar
  15. 15.
    Gehrke CW, Zumwalt RW, MC Cune RA et al. Quantitative high-performance liquid chromotography analysis of modified nucleosides in physiological fluids, tRNA and DNA. Recent Results Cancer Res 1983; 84:344–359.PubMedGoogle Scholar
  16. 16.
    Bird A, Southern EM. Use of restriction enzymes to study eukaryotic DNA methylation: I. The methylation pattern in ribosomal DNA from Xenopus Laevis. J Mol Biol 1978; 118:27–47.PubMedCrossRefGoogle Scholar
  17. 17.
    Cedar H, Solage A, Glaser G et al. Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. Nucleic Acids Res 1979; 6:2125–2132.PubMedCrossRefGoogle Scholar
  18. 18.
    Singer-Sam J, Lebon JM, Tanguay RL et al. A quantitative HpaII-PCR assay to measure methylation of DNA from a small number of cells. Nucl Acids Res 1990; 18:687–692.PubMedCrossRefGoogle Scholar
  19. 19.
    Baylin SB, Esteller M, Rountree MR et al. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 2001; 10:687–692.PubMedCrossRefGoogle Scholar
  20. 20.
    Counts JL, Goodman JI. Alterations in DNA methylation may play a variety of roles in carcinogenesis. Cell 1981; 83:13–15.CrossRefGoogle Scholar
  21. 21.
    Jones PA. DNA methylation errors and cancer. Cancer Res 1996; 56:2463–2467.PubMedGoogle Scholar
  22. 22.
    Fearon ER, Jones PA. Progressing toward a molecular description of colorectal cancer development. FASEB J 1992; 6:2783–2790.PubMedGoogle Scholar
  23. 23.
    Wahlfors J, Hiltunen H, Heinonen K et al. Genomic hypomethylation in human chronic lympho-cytic leukemia. Blood 1992; 80:2074–2080.PubMedGoogle Scholar
  24. 24.
    Cravo M, Pinto R, Fidalgo P et al. Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma. Gut 1996; 39:434–438.PubMedGoogle Scholar
  25. 25.
    Chen RZ, Petterson U, Beard C et al. DNA hypomethylation leads to elevated mutation rates. Nature 1998; 395:89–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Narayan A, Ji W, Zhang XY et al. Hypomethylation of pericentromeric DNA in breast adenocar-cinomas. Int J Cancer 1998; 77:833–838.PubMedCrossRefGoogle Scholar
  27. 27.
    Qu G, Dubeau L, Narayan A et al. Satellite DNA hypomethylation vs overall genomic hypomethylation in ovarian epithelial tumors of different malignant potentials. Mutation Research 1999; 423:91–101.PubMedGoogle Scholar
  28. 28.
    Stern LL, Mason JB, Selhub J et al. Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev 2000; 9:849–53.PubMedGoogle Scholar
  29. 29.
    Lin CH, Hsieh SY, Sheen IS et al. Genome-wide hypomethylation in hepatocellular carcinogenesis. Cancer Res 2001; 61:4238–43.PubMedGoogle Scholar
  30. 30.
    Baylin SB, Fearon ER, Vogelstein B et al. Hypermethylation of the 5′ region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies. Blood 1987; 70:412–417.PubMedGoogle Scholar
  31. 31.
    Makos M, Nelkin BD, Lerman MI et al. Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer. Proc Nalt Acad Sci USA 1992; 89:1929–1933.CrossRefGoogle Scholar
  32. 32.
    el-Deiry WS, Nelkin BD, Celano P et al. High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc Natl Acad Sci USA 1991; 88:3470–3474.PubMedCrossRefGoogle Scholar
  33. 33.
    Issa J-P, Vertino PM, Wu J. Increased cytosine DNA-methyltransferase activity during colon cancer progression. J Natl Cancer Inst 1993; 85:1235–1240.PubMedCrossRefGoogle Scholar
  34. 34.
    Melki JR, Warnecke P, Vincent PC et al. Increased DNA methyltransferase expression in leukaemia. Leukemia 1998; 12:311–316.PubMedCrossRefGoogle Scholar
  35. 35.
    Jakob CA, Guldenschuh I, Hürlimann R et al. 5′cytosine DNA-methyltransferase mRNA levels in hereditary colon carcinomas. Virchows Arc 1999; 434:57–62.CrossRefGoogle Scholar
  36. 36.
    Chen B, Liu X, Savell VH et al. Increased DNA methyltransferase expression in rhabdomyosarcomas. Int J Cancer 1999; 83:10–14.PubMedCrossRefGoogle Scholar
  37. 37.
    Feinberg AP, Vogelstein B. Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Com 1983; 111:47–54.PubMedCrossRefGoogle Scholar
  38. 38.
    Cheah MS, Wallace CD, Hoffman RM. Hypomethylation of DNA in cancer cells: A site-specific change in the c-myc oncogene. J Natl Cancer Inst 1984; 73:1057–1065.PubMedGoogle Scholar
  39. 39.
    Sharrard RM, Royds JA, Rogers S et al. Patterns of methylation of the c-myc gene in human colorectal cancer progression. Br J Cancer 1992; 65:667–672.PubMedGoogle Scholar
  40. 40.
    Nakayama M, Wada M, Harada T et al. Hypomethylation status of CpG sites at the promoter region, and overexpression of the human MDR1 gene in acute myeloid leukemias. Blood 1998; 2:4296–4307.Google Scholar
  41. 41.
    Tao L, Yang S, Xie M et al. Hypomethylation and overexpression of c-jun and c-myc protooncogenes and increased DNA methyltransferase activity in dichloroacetic and trichloroacetic acid-promoted mouse liver tumors. Cancer Letters 2000; 158:185–193.PubMedCrossRefGoogle Scholar
  42. 42.
    Greger V, Debus N, Lohman D et al. Frequency and parental origin of hypermethylated Rb1 alleles in retinoblastoma. Human Genet 1994; 94:491–496.CrossRefGoogle Scholar
  43. 43.
    Greenblatt MS, Bennett WP, Hollstein M et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994; 54:4855–4878.PubMedGoogle Scholar
  44. 44.
    Magewu AN, Jones PA. Ubiquitous and tenacious methylation of the CpG site in codon 248 of the p53 gene may explain ist frequent appearance as a mutational hot spot in human cancer. Mol Cell Biol 1994; 14:4225–4232.PubMedGoogle Scholar
  45. 45.
    Gonzalez-Zuleta M, Bender CM, Yang AS et al. Methylation of the 5′ CpG island of the pl6/CDKN2 tumor-suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res 1995; 55:4531–4535.Google Scholar
  46. 46.
    Herman JG, Merlo A, Mao L et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all human common cancers. Cancer Res 1995; 55:4525–4530.PubMedGoogle Scholar
  47. 47.
    Little M, Wainwright B. Methylation and p16: Suppressing the suppressor. Nature Med 1995; 1:633–634.PubMedCrossRefGoogle Scholar
  48. 48.
    Merlo A, Herman JG, Mao L et al. 5′ CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/CDKN2/MTS1 in human cancers. Nature Med 1995; 1:686–692.PubMedCrossRefGoogle Scholar
  49. 49.
    Dodge JE, List AF, Futscher BW. Selective variegated methylation of the p15 CpG island in acute myeloid leukaemia. Int J Cancer 1998; 78:561–567.PubMedCrossRefGoogle Scholar
  50. 50.
    Esteller M, Sanchez-Cespedes M, Rosell R et al. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from nonsmall cell lung cancer patients. Cancer Res 1999; 59:67–70.PubMedGoogle Scholar
  51. 51.
    Dammann R, Yang G, Pfeifer GP. Hypermethylation of the cpG island of Ras association domain family lA(RASSFlA), a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large percentage of human breast cancers. Cancer Res 2001; 61:3105–3109.PubMedGoogle Scholar
  52. 52.
    Baldwin RL, Nemeth E, Tran H et al. BRCA1 promoter region hypermethylation in ovarian carcinoma: A population-based study. Cancer Res 2000; 60:5329–5333.PubMedGoogle Scholar
  53. 53.
    Sanchez-Cespedes M, Esteller M, Wu L et al. Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res 2000; 60:892–895.PubMedGoogle Scholar
  54. 54.
    Esteller M. Epigenetic lesions causing genetic lesions in human cancer: Promoter hypermethylation of DNA repair genes. Eur J Cancer 2000; 36:2294–2300.PubMedCrossRefGoogle Scholar
  55. 55.
    Lehmann U, Hasemeier B, Lilischkis R et al. Quantitative analysis of promoter hypermethylation in laser-microdissected archival specimens. Lab Invest 2001; 1:635–638.Google Scholar
  56. 56.
    Erlanger BF, Beiser SM. Antibodies specific for ribonucleosides and ribonucleotides and their reaction with DNA. Proc Natl Acad Sci USA 1964; 52:68–74.PubMedCrossRefGoogle Scholar
  57. 57.
    Beiser SM, Erlanger BF, Tanenbaum SW. Conjugated and synthetic antigens: Preparation of purine-and pyrimidine-protein conjugates. In: Williams CA, Chase MW, eds. Methods in Immunol-ogy and Immunochemistry. New York: Academic Press, 1967:180–185.Google Scholar
  58. 58.
    Schrek RR, Erlanger BF, Miller OJ. The use of antinucleoside antibodies to probe the organization of chromosomes denatured by ultraviolet organization. Exp Cell Res 1974; 88:31–39.CrossRefGoogle Scholar
  59. 59.
    Miller OJ, Schnedl W, Allen J et al. 5-methylcytosine localised in mammalian heterochromatin. Nature 1974; 251:636–637.PubMedCrossRefGoogle Scholar
  60. 60.
    Waalkes TP, Gehrke CW, Bleyer WA et al. The urinary excretion of nucleosides of tRNA in patients with advanced cancer. Cancer 1975; 36:390–397.PubMedCrossRefGoogle Scholar
  61. 61.
    Borek E, Baliga BS, Gehrke CW et al. High turnover of tRNA in tumor tissue. Cancer Res 1977; 37:398–402.Google Scholar
  62. 62.
    Speer J, Gehrke CW, Kuo KC et al. tRNA breakdown products as markers for cancer. Cancer 1979; 44:2120–2123.PubMedCrossRefGoogle Scholar
  63. 63.
    Thomale J, Nass G. Elevated urinary excretion of RNA catabolites as an early signal of tumor development in mice. Cancer Lett 1982; 15:149–159.PubMedCrossRefGoogle Scholar
  64. 64.
    Reynaud C, Bruno C, Boullanger P et al. Monitoring of urinary excretion of modified nucleosides in cancer patients using a set of six monoclonal antibodies. Cancer Lett 1991; 61:255–262.CrossRefGoogle Scholar
  65. 65.
    Dante R, Baldini A, Miller DA et al. Methylation of the 5′ flanking sequences of the ribosomal DNA in human cell lines and in a human-hamster hybrid cell line. J Cell Biochem 1992; 50:357–362.PubMedCrossRefGoogle Scholar
  66. 66.
    Montpellier C, Bourgeois C, Kokalj-Vokac N et al. Detection of methylcytosine rich heterochromatin on banded chromosomes. Application to cells with various status of DNA methylation. Cancer Genet Cytogenet 1994; 78:87–93.PubMedCrossRefGoogle Scholar
  67. 67.
    Barbin A, Montpellier C, Kokalj-Vokac N et al. In situ DNA methylation analysis of human tumor cells: Mapping of methylcytosine-rich bands. Human Genetics 1994; 94:684–692.PubMedCrossRefGoogle Scholar
  68. 68.
    Miniou P, Jeanpierre M, Blanquet V et al. Abnormal methylation pattern in constitutive and facultative (X inactive chromosome) heterochromatin of ICF patients. Human Mol Genetics 1994; 3:2093–2102.CrossRefGoogle Scholar
  69. 69.
    Counts J, Goodman JI. Hypomethylation of DNA: An epigenetic mechanism involved in tumor promotion. Mol Carcinog 1994; 11:185–188.PubMedCrossRefGoogle Scholar
  70. 70.
    Schmutte C, Yang AS, TuDung T et al. Mechanisms for the involvement of DNA methylation in colon carcinogenesis. Cancer Res 1996; 56:2375–2381.PubMedGoogle Scholar
  71. 71.
    Lengauer C, Kinzler KW, Vogelstein B. DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci USA 1997; 94:2545–2550.PubMedCrossRefGoogle Scholar
  72. 72.
    Ahuja N, Mohan AL, Li Q et al. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Res 1997; 57:3370–3374.PubMedGoogle Scholar
  73. 73.
    Steinbeck RG. Chromosome division figures reveal genomic instability in tumorigenesis of human colon mucosa. Brit J Cancer 1998; 77:1027–1034.PubMedGoogle Scholar
  74. 74.
    Cunningham JM, Christensen ER, Tester DJ et al. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 1998; 58:3455–3460.PubMedGoogle Scholar
  75. 75.
    Xu G, Bestor TH, Bourc’his D et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 1999; 402:187–191.PubMedCrossRefGoogle Scholar
  76. 76.
    Shannon B, Kay P, House A et al. Hypermethylation of the Myf-3 gene in colorectal cancers: Associations with pathological features and with microsatellite instability. Int J Cancer 1999; 84:109–113.PubMedCrossRefGoogle Scholar
  77. 77.
    Vilain A, Bernardino J, Gerbault-Seureau M et al. DNA methylation and chromosome instability in lymphoblastoid cell lines. Cytogenet Cell Genet 2000; 90:93–101.PubMedCrossRefGoogle Scholar
  78. 78.
    Lewis J, Bird A. DNA methylation and chromatin structure. FEBS Lett 1991; 285:155–159.PubMedCrossRefGoogle Scholar
  79. 79.
    Laird PW, Jaenisch R. The role of DNA methylation in cancer Genetics and epigenetics. Annu Rev Genet 1996; 30:441–464.PubMedCrossRefGoogle Scholar
  80. 80.
    Laird PW. Oncogenic mechanisms mediated by DNA methylation. Molecular Medicine today 1997:223–229.Google Scholar
  81. 81.
    Weissbach A, Ward C, Bolden A. Eukaryotic DNA methylation and gene expression. Curr Topics Cell Regul 1989; 30:1–21.Google Scholar
  82. 82.
    Carr BI, Reilly JG, Smith SS et al. The tumorigenicity of 5-azacytidine in the male Fischer rat. Carcinogenesis 1984; 5:1583–1590.PubMedCrossRefGoogle Scholar
  83. 83.
    Cavaliere A, Bufalari A, Vitali R. 5-Azacytidine carcinogenesis in BALB/c mice. Cancer Lett 1987; 37:51–58.PubMedCrossRefGoogle Scholar
  84. 84.
    Kerbel RS, Frost P, Liteplo R et al. Possible epigenetic mechanisms of tumor progression: Induction of high-frequency heritable but phenotypically unstable changes in the tumorigenic and metastatic properties of tumor cell populations by 5-azacytidine treatment. J Cell Physiol 1984; 3:87–97.CrossRefGoogle Scholar
  85. 85.
    Ormerod EJ, Everett CA, Hart IR. Enhanced experimental metastatic capacity of a human tumor cell line following treatment with 5-azacytidine. Cancer Res 1986; 46:884–890.PubMedGoogle Scholar
  86. 86.
    de Capoa A, Grappelli C, Febbo FR et al. Methylation levels of normal and chronic lymphocytic leukemia B lymphocytes: Computer-assisted quantitative analysis of anti-5-methylcytosine antibody binding to individual nuclei. Cytometry 1999; 36:157–159.PubMedCrossRefGoogle Scholar
  87. 87.
    de Capoa A, Di Leandro M, Grappelli C et al. Methylation status of individual interphase nuclei in human cultured cells: A semiquantitative computerised analysis. Cytometry 1998; 31:85–92.PubMedCrossRefGoogle Scholar
  88. 88.
    de Capoa A, Romana Febbo F, Giovanelli F et al. Reduced levels of Poly(ADP)-ribosylation result in chromatin compaction and hypermethylation as shown by a cell-by-cell computer-assited quantitative analysis. FASEB J 1999; 13:89–93.PubMedGoogle Scholar
  89. 89.
    Piyathilake CJ, Johanning GL, Frost AR et al. Immunohistochemical evaluation of global DNA methylation: Comparison wit in vitro radiolabeled methyl incorporation assay. Biotechnic and Histochemistry 2000; 75:251–258.PubMedGoogle Scholar
  90. 90.
    Piyathilake CJ, Frost AR, Bell WC et al. Altered global methylation of DNA: An epigenetic difference in susceptibility for lung cancer is associated with its progression. Human Pathol 2001; 32:856–62.CrossRefGoogle Scholar
  91. 91.
    Soares J, Pinto AE, Cunha CV et al. Global DNA hypomethylation in breast carcinoma: Correlation with prognostic factors and tumor progression. Cancer 1999; 85:112–118.PubMedCrossRefGoogle Scholar
  92. 92.
    Piyathilake CJ, Macaluso M, Henao O et al. Race and age dependant differences in global methylation of DNA. FASEB J 2001; 15:494–12.Google Scholar
  93. 93.
    Mayer W, Niveleau A, Walter J et al. Demethylation of the zygotic paternal genome. Nature 2000; 403:501–502.PubMedGoogle Scholar
  94. 94.
    Sano H, Royer HD, Sager R. Identification of 5-methylcytosine in DNA fragments immobilized on nitrocellulose paper. Proc Natl Acad Sci USA 1980; 77:3581–3585.PubMedCrossRefGoogle Scholar
  95. 95.
    Sano H, Imokawa M, Sager R. Detection of heavy methylation in human repetitive DNA subsets by a monoclonal antibody against 5-methylcytosine. Biochim Biophys Acta 1988; 951:157–165.PubMedGoogle Scholar
  96. 96.
    Bernardino J, Roux C, Almeida A et al. DNA hypomethylation in breast cancer: An independent parameter of tumor progression? Cancer Genet Cytogenet 1997; 97:83–89.PubMedCrossRefGoogle Scholar
  97. 97.
    Drouet E, Brousset P, Fares F et al. High Epstein-Barr virus (EBV) serum load and elevated titers of anti-zebra antibodies in patients with EBV-harboring tumor cells of Hodgkin’s disease. J Med Virol 1999; 57:383–389.PubMedCrossRefGoogle Scholar
  98. 98.
    Yang X, Yan L, Davidson NE. DNA methylation in breast cancer. Endocr Relat Cancer 2001; 8:115–127.PubMedCrossRefGoogle Scholar
  99. 99.
    Habib M, Fares F, Bella C et al. DNA global hypomethylation in EBV-transformed interphase nuclei. Exp Cell Res 1999; 249:46–53.PubMedCrossRefGoogle Scholar
  100. 100.
    Hernandez-Blazquez FJ, Habib M, Dumollard JM et al. Evaluation of global DNA hypomethylation in human colon cancer tissues by immunohistochemistry and image analysis. Gut 2000; 47:689–693.PubMedCrossRefGoogle Scholar
  101. 101.
    Hakkarainen M, Wahlfors J, Myohannen S et al. Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing. Int J Cancer Pred Oncol 1996; 69:471–474.CrossRefGoogle Scholar
  102. 102.
    Huang TH, Perry MR, Laux DE. Methylation profiling of CpG islands in human breast cancer cells. Human Mol Genet 1999; 8:459–470.CrossRefGoogle Scholar
  103. 103.
    Wang K, Gan L, Jeffery E et al. Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray. Gene 1999; 229:101–108.PubMedCrossRefGoogle Scholar
  104. 104.
    Costello JF, Fruhwald MC, Smiraglia DJ et al. Aberrant CpG-island methylation has nonrandom and tumor-type-specific patterns. Nat Genet 2000; 24:132–138.PubMedCrossRefGoogle Scholar
  105. 105.
    Yan PS, Chen CM, Shi H et al. Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays. Cancer Res 2001; 61:8375–8380.PubMedGoogle Scholar
  106. 106.
    Tycko B, Ashkenas J. Epigenetics and its role in disease. J Clin Invest 2000; 105:245–246.PubMedCrossRefGoogle Scholar
  107. 107.
    Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000; 1:11–19.PubMedCrossRefGoogle Scholar
  108. 108.
    Warnecke PM, Bestor TH. Cytosine methylation and human cancer. Curr Opin Oncol 2000; 12:68–73.PubMedCrossRefGoogle Scholar
  109. 109.
    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.PubMedCrossRefGoogle Scholar
  110. 110.
    Feinberg AP. Cancer epigenetics takes center stage. Proc Natl Acad Sci USA 2001; 98:392–394.PubMedCrossRefGoogle Scholar
  111. 111.
    Robertson KD. DNA methylation, methyltransferases and cancer. Oncogene 2001; 20:3139–3155.PubMedCrossRefGoogle Scholar
  112. 112.
    Herman JG, Baylin SB. Promoter-region hypermethylation and gene silencing in human cancer. Curr Top Microbiol Immunol 2000; 249:35–54.PubMedGoogle Scholar
  113. 113.
    Esteller M, Corn PG, Baylin SB et al. A gene hypermethylation profile of human cancer. Cancer Res 2001; 61:3225–3229.PubMedGoogle Scholar
  114. 114.
    Leonhardt H, Page AW, Weier HU et al. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 1992; 71:865–873.PubMedCrossRefGoogle Scholar
  115. 115.
    Schubeler D, Lorincz MC, Cimbora DM et al. Genomic targeting of methylated DNA: Influence of methylation on transcription, replication, chromatin structure, and histone acetylation. Mol Cell Biol 1992; 20:9103–9112.CrossRefGoogle Scholar
  116. 116.
    Leonhardt H, Cardoso MC. DNA methylation, nuclear structure gene expression and cancer. J. Cell Biochem 2000; 35(Suppl):78–83.CrossRefGoogle Scholar
  117. 117.
    Baylin SB, Esteller M, Rountree MR et al. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 2001; 10:687–92.PubMedCrossRefGoogle Scholar
  118. 118.
    Esteller M, Herman JG. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumors. J Pathol 2002; 196:1–7.PubMedCrossRefGoogle Scholar

Copyright information

© Eurekah.com and Kluwer Academic/Plenum Publishers 2005

Authors and Affiliations

  • Alain Niveleau
    • 1
  • Chandrika Piyathilake
    • 2
  • Adriana de Capoa
    • 3
  • Claudio Grappelli
    • 4
  • Jean-Marc Dumollard
    • 5
  • Lucien Frappart
    • 6
  • Emmanuel Drouet
    • 7
  1. 1.Laboratoire de Virologie Structurale et Moleculaire Faculte de MedecineUniversite Joseph Fourier de GrenobleLa TroncheFrance
  2. 2.Department of Nutrition Sciences Division of Nutritional Biochemistry and Molecular BiologyUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Dipartimento di Genetica e Biologia MolecolareUniversita di RomaRoamItaly
  4. 4.Dipartimento di Genetica e Biologia MolecolareUniversita di Roma 1 La SapienzaRomeItaly
  5. 5.Service d’Anatomie et de Cytologie PathologiquesHopital BellevueSaint-EtienneFrance
  6. 6.Unit INSERM 403Facult de M decine LaennecLyonFrance
  7. 7.Laboratoire de Virologie Moleculaire et Sturcturale Faculte de M decine et PharmacieUniversit Joseph Fourier de GrenobleLa TroncheFrance

Personalised recommendations