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Cancer Epigenetics: DNA Methylation and Chromatin Alterations in Human Cancer

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Book cover New Trends in Cancer for the 21st Century

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 532))

Abstract

Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of human cancer One of the most characteristic changes is the hypermethylation of CpG islands of tumor suppressor genes associated with their transcriptional silencing The target genes are distributed in all cellular pathways (apoptosis, DNA repair, cell cycle, cell adherence, etc) They are “classical” tumor suppressor genes with associated familial cancers (BRCA1, hMLH1, p16lNK4aVHL, etc) and putative new tumor suppressor genes which loss may contribute to the transformed phenotype (MGMT, p14ARF, GSTP1, RARB2, etc) A tumor-type specific profile of CpG island hypermethylation exist in human cancer that allows the use of these aberrantly hypermethylated loci as biomarkers of the malignant disease The irruption of new technologies for the careful study of the DNA methylation patterns, and their genetic partners in accomplishing gene silencing, it may also provide us with new drugs for the epigenetic treatment of human tumors

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References

  1. Bird, AP CpG-rich islands and the function of DNA methylation Nature 1986, 321:209–213

    Article  PubMed  CAS  Google Scholar 

  2. Nguyen C, Liang G Nguyen TT, Tsao-Wei D, Groshen S, Lubbert M, Zhou JH, Benedict WF, Jones PA Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cells J Nail Cancer Inst 2001, 93,1465–72

    Article  CAS  Google Scholar 

  3. Esteller, M, Corn, PG, Baylin, SB, and Herman, JG A gene hypermethylation profile of human cancer Cancer Res, 2001, 61, 3225–3229

    PubMed  CAS  Google Scholar 

  4. Greger V, Passarge E, Hopping W, Messmer E, Horsthernke B Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma Hum Genet 1989, 83,155–8

    Article  PubMed  CAS  Google Scholar 

  5. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma Proc Natl Acad Sci U S A 1994, 91,9700–4

    Article  PubMed  CAS  Google Scholar 

  6. Merlo, A Herman, JG, Mao, L, Lee, DJ, Gabrielson, E, Burger, PC, Baylin, SB, and Sidransky, D 5 CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers Nat Med 1995, 1: 686–692

    Article  PubMed  CAS  Google Scholar 

  7. Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers Cancer Res 1995, 55,4525–30

    PubMed  CAS  Google Scholar 

  8. Gonzalez-Zulueta, M, Bender, CM, Yang, AS, Nguyen, T, Beart, RW, Van Tornout, JM, and Jones PA Methylation of the 5’ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing

    Google Scholar 

  9. Clark, SJ, J Harrison, CL Paul and M Frommer High sensitivity mapping of methylated cytosines Nucleic Acids Res 1994, 22:2990–2997

    Article  PubMed  CAS  Google Scholar 

  10. 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 U S A 1996, 93,9821–6

    Article  PubMed  CAS  Google Scholar 

  11. Esteller M, Fraga MF, Guo M, Garcia-Foncillas J, Hedelfank I, Godwin AK, Trojan J, Vaurs-Barrière C, Bignon Y-J, Ramus S, Benitez J, Akiyama Y, Caldes T, Canal MJ, Rodriguez R, Capella G, Peinado MA, Borg A, Aaltonen LA, Ponder BA, Baylin SB, Herman JG DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis Human Molecular Genetics, 2001, 10, 3001–7

    Article  PubMed  CAS  Google Scholar 

  12. Myohanen SK, Baylin SB, Herman JG Hypermethylation can selectively silence individual pl6ink4A alleles in neoplasia Cancer Res 1998, 58,591–3

    PubMed  CAS  Google Scholar 

  13. Herman, JG, Umar, A, Polyak, K, Graft, JR, Ahuja, N, Issa, JP, Markowitz, S, Willson, JK, Hamilton, SR, Kinzler, KW, Kane, MF, Kolodner, RD, Vogelstein, B, Kunkel, TA, and Baylin, SB Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma Proc Natl Acad Sci U S A 1998, 95: 6870–6875

    Article  PubMed  CAS  Google Scholar 

  14. Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas Oncogene, 1998,17,2413–2417

    Article  PubMed  CAS  Google Scholar 

  15. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG Inactivation of the DNA repair gene 06methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia Cancer Research, 1999, 59, 793–797

    PubMed  CAS  Google Scholar 

  16. Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS, Hsieh WS, Isaacs WB, Nelson WG Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis Proc Natl Acad Sci U S A 1994, 91,11733–7

    Article  PubMed  CAS  Google Scholar 

  17. Esteller M, Corn PG, Urena JM, Gabrielson E, Baylin SB, Herman JG Inactivation of glutathione Stransferase P1 gene by promoter hypermethylation in human neoplasia Cancer Research, 1998, 58, 4515–4518

    PubMed  CAS  Google Scholar 

  18. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Bussaglia E, Lerma E, Prat J, Harkes IC, Repasky EA, Gabrielson E, Schutte M, Baylin SB, Herman JG Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors Journal of the National Cancer Institute 2000, 92, 5649

    Article  Google Scholar 

  19. Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S, Pelicci PG Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor Science 2002, 295, 1079–1082

    Article  PubMed  CAS  Google Scholar 

  20. Esteller M, Fraga MF, Paz MF, Campo E, Colomer D, Novo FJ, Calsanz MJ, Galm 0, Guo M, Benitez J, Herman JG Cancer epigenetics and methylation Science 2002, 297, 1807–1808

    Article  PubMed  Google Scholar 

  21. Paz MF, Avila S, Fraga MF, Pollan M, Capella G, Peinado MA, Sanchez-Cespedes M, Herman JG, Esteller M Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors Cancer Res 2002, 62, 4519–4524

    PubMed  CAS  Google Scholar 

  22. Jones PA, Laird PW Cancer epigenetics comes of age Nat Genet 1999, 21,163–7

    Article  PubMed  CAS  Google Scholar 

  23. Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer Hum Mol Genet 2001, 10, 687–92

    Article  PubMed  CAS  Google Scholar 

  24. Graff JR, Herman JG, Myohanen S, Baylin SB, Vertino PM Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation J Biol Chem 1997, 272: 22322–9

    Article  PubMed  CAS  Google Scholar 

  25. Song JZ, Stirzaker C, Harrison J, Melki JR, Clark SJ Hypermethylation trigger of the glutathione-Stransferase gene (GSTPI) in prostate cancer cells Oncogene 2002, 21, 1048–61

    Article  PubMed  CAS  Google Scholar 

  26. Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA xThe human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors Nucleic Acids Res 1999, 27,2291–8

    CAS  Google Scholar 

  27. Feinberg AP, Vogelstein B Hypomethylation distinguishes genes of some human cancers from their normal counterparts Nature 1983, 301,89–92

    Article  PubMed  CAS  Google Scholar 

  28. Ehrlich M DNA hypomethylation and cancer In: DNA alterations in cancer: genetic and epigenetic changes Edited by Melanie Ehrlich, Eaton Publishing, Natick, Pages 273–291, 2000

    Google Scholar 

  29. Keshet, I, Lieman-Hurwitz, J and Cedar, H DNA methylation affects the formation of active chromatin Cell 1986, 44, 535–543

    Article  PubMed  CAS  Google Scholar 

  30. Lewis, JD, Meehan, RR, Henzel, WJ, Maurer-Fogy, I, Jeppesen, P, Klein, F and Bird A Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA Cell 1992, 69, 905–914

    Article  PubMed  CAS  Google Scholar 

  31. Magdinier, F and Wolffe, AP Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasia Proc Natl Acad Sci USA 2001, 98, 4990–4995

    Article  PubMed  CAS  Google Scholar 

  32. Nan, X, Ng, HH, Johnson, CA, Laherty, CD, Turner, BM, Eisenman, RN and Bird A Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex Nature 1998, 393, 386–389

    Article  PubMed  CAS  Google Scholar 

  33. Jones, PL, Veenstra, GJ, Wade, PA, Vermaak, D, Kass, SU, Landsberger, N, Strouboulis, J and Wolffe, AP Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription Nat Genet, 1989, 19, 187–191

    Article  Google Scholar 

  34. Ballestar E and Esteller M The impact of chromatin in human cancer: linking DNA methylation to gene silencing Carcinogenesis 2002, 23: 1103–9

    Article  PubMed  CAS  Google Scholar 

  35. 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 Research, 1999, 59, 67–70

    PubMed  CAS  Google Scholar 

  36. Tang X, Khuri FR, Lee JJ, Kemp BL, Liu D, Hong WK, Mao L Hypermethylation of the death-associated protein (DAP) kinase promoter and aggressiveness in stage I non-small-cell lung cancer J Nat! Cancer Inst 2000, 92,1511–6

    Article  PubMed  CAS  Google Scholar 

  37. Esteller M, Gonzalez S, Risques RA, Marcuello E, Mangues R, Germa JR, Herman JG, Capella G, Peinado MA K-ras and p16 aberrations confer poor prognosis in human colorectal cancer J Clin Oncol, 2001,19, 299–304

    PubMed  CAS  Google Scholar 

  38. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents N Engl J Med, 2000, 343, 1350–1354

    Article  PubMed  CAS  Google Scholar 

  39. Esteller M, Gaidano G, Goodman SN, Zagonel V, Capello D, Botto B, Rossi D, Gloghini A, Vitolo U, Carbone A, Baylin SB, Herman JG Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma J Nat! Cancer Inst 2002, 94, 6–7

    Article  Google Scholar 

  40. Wijermans PW, Krulder JW, Huijgens PC, Neve P Continuous infusion of low-dose 5-Aza-2’deoxycytidine in elderly patients with high-risk myelodysplastic syndrome Leukemia 1997, 11,1–5

    Article  PubMed  CAS  Google Scholar 

  41. Schwartsmann G, Fernandes MS, Schaan MD, Moschen M, Gerhardt LM, Di Leone L, Loitzembauer B, Kalakun L Decitabine (5-Aza-2’-deoxycytidine; DAC) plus daunorubicin as a first line treatment in patients with acute myeloid leukemia: preliminary observations Leukemia 1997, 11 Suppl 1:528–31

    Google Scholar 

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Authors and Affiliations

  1. Cancer Epigenetics Laboratory, Spanish National Cancer Center (CNIO), Melchor Fernandez Almagro 3, Madrid, 28029, Spain

    Manel Esteller

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  1. Manel Esteller
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Editors and Affiliations

  1. University of Valencia, Valencia, Spain

    Antonio Llombart-Bosch

  2. Valencian Foundation for Biomedical Research, Valencia, Spain

    Vicente Felipo

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Esteller, M. (2003). Cancer Epigenetics: DNA Methylation and Chromatin Alterations in Human Cancer. In: Llombart-Bosch, A., Felipo, V. (eds) New Trends in Cancer for the 21st Century. Advances in Experimental Medicine and Biology, vol 532. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0081-0_5

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  • DOI: https://doi.org/10.1007/978-1-4615-0081-0_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4914-3

  • Online ISBN: 978-1-4615-0081-0

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