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The Role of Epigenetics in Cancer: From Molecular Function to High-Throughput Assays

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Diagnostic, Prognostic and Therapeutic Value of Gene Signatures

Part of the book series: Current Clinical Pathology ((CCPATH))

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Abstract

The notion of epigenetics encompasses various modifications of chromatin, including DNA methylation and post-translational modifications of histone proteins that can be stably transmitted through mitosis. Epigenetics plays a fundamental role in normal cell physiology as it is molecularly involved in virtually all chromatin-associated processes, including gene expression, DNA replication and repair. Alterations in the global profile of epigenetic modifications are commonly observed in cancer and are believed to be associated with the establishment and clonal maintenance of an aberrant gene expression pattern. Recent technological advances have enabled to assess the epigenetic signature of a given cell type in a genome-wide manner. These comparative epigenome studies have significantly increased our understanding of the oncogenic process. In addition, they constitute promising tools for improved classification and diagnosis of cancer patients, ultimately leading to the design of personalised therapies. In this chapter, we focus on the role of epigenetics in normal and pathological cell development. We outline recent large-scale assays of epigenetic profiling in normal and cancer tissue samples as well as pertinent new discoveries linking epigenetics and cancer.

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References

  1. Golub TR. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999;286(5439):531–7.

    Article  PubMed  CAS  Google Scholar 

  2. Gal-Yam EN, Egger G, Iniguez L, et al. Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. Proc Natl Acad Sci USA. 2008;105(35):12979–84.

    Article  PubMed  Google Scholar 

  3. Neff T, Armstrong SA. Chromatin maps, histone modifications and leukemia. Leukemia. 2009;23(7):1243–51.

    Article  PubMed  CAS  Google Scholar 

  4. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Genet. 2007;8(4):286–98.

    CAS  Google Scholar 

  5. Kaiser J. Epigenetic drugs take on cancer. Science. 2010;330(6004):576–8.

    Article  PubMed  CAS  Google Scholar 

  6. Bird A. Perceptions of epigenetics. Nature. 2007;447(7143):396–8.

    Article  PubMed  CAS  Google Scholar 

  7. Meissner A. Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol. 2010;28(10):1079–88.

    Article  PubMed  CAS  Google Scholar 

  8. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    Article  PubMed  CAS  Google Scholar 

  9. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057–68.

    Article  PubMed  CAS  Google Scholar 

  10. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31(2):89–97.

    Article  PubMed  CAS  Google Scholar 

  11. Cedar H, Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009;10(5):295–304.

    Article  PubMed  CAS  Google Scholar 

  12. Bock C, Walter J, Paulsen M, Lengauer T. CpG island mapping by epigenome prediction. PLoS Comput Biol. 2007;3(6):e110.

    Article  PubMed  CAS  Google Scholar 

  13. Takai D, Jones P. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA. 2002;99(6):3740–5.

    Article  PubMed  CAS  Google Scholar 

  14. Ooi SKT, Bestor TH. The colorful history of active DNA demethylation. Cell. 2008;133(7):1145–8.

    Article  PubMed  CAS  Google Scholar 

  15. Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5.

    Article  PubMed  CAS  Google Scholar 

  16. Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327(5971):1345–50.

    Article  PubMed  CAS  Google Scholar 

  17. Langemeijer SMC, Aslanyan MG, Jansen JH. TET proteins in malignant hematopoiesis. Cell Cycle. 2009;8(24):4044–8.

    Article  PubMed  CAS  Google Scholar 

  18. Rakyan VK, Down T, Thorne NP, et al. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res. 2008;18(9):1518–29.

    Article  PubMed  CAS  Google Scholar 

  19. Ball MP, Li JB, Gao Y, et al. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27(4):361–8.

    Article  PubMed  CAS  Google Scholar 

  20. Kacem S, Feil R. Chromatin mechanisms in genomic imprinting. Mamm Genome. 2009;20(9–10):544–56.

    Article  PubMed  CAS  Google Scholar 

  21. Thomson JP, Skene PJ, Selfridge J, et al. CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature. 2010;464(7291):1082–6.

    Article  PubMed  CAS  Google Scholar 

  22. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 1999;98(3):285–94.

    Article  PubMed  CAS  Google Scholar 

  23. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293(5532):1074–80.

    Article  PubMed  CAS  Google Scholar 

  24. Holliday. Epigenetic defects, assisted reproductive technology, and clinical practice: a call for clinicians and genetic counselors. Clin Genet. 1987;22(5):133–482.

    Google Scholar 

  25. Glasspool RM, Teodoridis JM, Brown R. Epigenetics as a mechanism driving polygenic clinical drug resistance. Br J Cancer. 2006;94(8):1087–92.

    Article  PubMed  CAS  Google Scholar 

  26. Christensen BC, Houseman EA, Marsit CJ, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009;5(8):e1000602.

    Article  PubMed  CAS  Google Scholar 

  27. Marsit CJ. Promoter hypermethylation is associated with current smoking, age, gender and survival in bladder cancer. Carcinogen. 2007;28(8):1745–51.

    Article  CAS  Google Scholar 

  28. Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell. 2007;128(4):669–81.

    Article  PubMed  CAS  Google Scholar 

  29. Schones DE, Zhao K. Genome-wide approaches to studying chromatin modifications. Nat Genet. 2008;9(3):179–91.

    CAS  Google Scholar 

  30. Lister R, Ecker JR. Finding the fifth base: Genome-wide sequencing of cytosine methylation. Genome Res. 2009;19(6):959–66.

    Article  PubMed  CAS  Google Scholar 

  31. Brunner AL, Johnson DS, Kim SW, et al. Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver. Genome Res. 2009;19(6):1044–56.

    Article  PubMed  CAS  Google Scholar 

  32. Irizarry R, Ladd-Acosta C, Carvalho B, et al. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res. 2008;18(5):780–90.

    Article  PubMed  CAS  Google Scholar 

  33. Weber M, Davies JJ, Wittig D, et al. Chromosome-wide and promoter-specific analyses identify sites of ­differential DNA methylation in normal and transformed human cells. Nat Genet. 2005;37(8):853–62.

    Article  PubMed  CAS  Google Scholar 

  34. Brinkman AB, Simmer F, Ma K, et al. Whole-genome DNA methylation profiling using MethylCap-seq. Methods. 2010;52(3):232–6.

    Article  PubMed  CAS  Google Scholar 

  35. Keshet I, Schlesinger Y, Farkash S, et al. Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet. 2006;38(2):149–53.

    Article  PubMed  CAS  Google Scholar 

  36. Weber M, Hellmann I, Stadler MB, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39(4):457–66.

    Article  PubMed  CAS  Google Scholar 

  37. Ruike Y, Imanaka Y, Sato F, Shimizu K, Tsujimoto G. Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing. BMC Genomics. 2010;11:137.

    Article  PubMed  CAS  Google Scholar 

  38. Martens JH et al. PML-RARalpha/RXR alters the epigenetic landscape in acute promyelocytic lekumia. Cancer Cell. 2010;17(2):173–85.

    Article  PubMed  CAS  Google Scholar 

  39. Jia J, Pekowska A, Jaeger S, et al. Assessing the efficiency and significance of methylated DNA immunoprecipitation (MeDIP) assays in using in vitro methylated genomic DNA. BMC Res Notes. 2010;3:240.

    Article  PubMed  CAS  Google Scholar 

  40. Pelizzola M, Koga Y, Urban AE, et al. MEDME: an experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment. Genome Res. 2008;18(10):1652–9.

    Article  PubMed  CAS  Google Scholar 

  41. Laurent L, Wong E, Li G, et al. Dynamic changes in the human methylome during differentiation. Genome Res. 2010;20(3):320–31.

    Article  PubMed  CAS  Google Scholar 

  42. Meissner A, Mikkelsen TS, Gu H, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008;454(7205):766–70.

    PubMed  CAS  Google Scholar 

  43. Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462(7271):315–22.

    Article  PubMed  CAS  Google Scholar 

  44. Gu H, Bock C, Mikkelsen TS, et al. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution. Nat Genet. 2010;7(2):133–6.

    Article  CAS  Google Scholar 

  45. Hodges E, Smith AD, Kendall J, et al. High definition profiling of mammalian DNA methylation by array ­capture and single molecule bisulfite sequencing. Genome Res. 2009;19(9):1593–605.

    Article  PubMed  CAS  Google Scholar 

  46. Bock C, Tomazou EM, Brinkman AB, et al. Quantitative comparison of genome-wide DNA methylation ­mapping technologies. Nat Biotechnol. 2010;28:1106–14.

    Article  PubMed  CAS  Google Scholar 

  47. Jones P, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Genet. 2002;3(6):415–28.

    CAS  Google Scholar 

  48. Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science. 1985;228(4696):187–90.

    Article  PubMed  CAS  Google Scholar 

  49. Feinberg AP, Kuo KC. Reduced genomic 5-Methylcytosine content in human colonic neoplasi and content as afraction of total. Cancer Res. 1988;48(5):1159–61.

    PubMed  CAS  Google Scholar 

  50. Yoder J, Walsh CP, Bestor TH. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 1997;13(8):335–40.

    Article  PubMed  CAS  Google Scholar 

  51. Xu GL, Bestor TH, Bourc’his D, et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature. 1999;402(6758):187–91.

    Article  PubMed  CAS  Google Scholar 

  52. Gaudet F, Hodgson JG, Eden A, et al. Induction of tumors in mice by genomic hypomethylation. Science. 2003;300(5618):489–92.

    Article  PubMed  CAS  Google Scholar 

  53. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300(5618):455.

    Article  PubMed  CAS  Google Scholar 

  54. Dodge JE, Okano M, Dick F, et al. Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation, chromosomal instability, and spontaneous immortalization. J Biol Chem. 2005;280(18):17986–91.

    Article  PubMed  CAS  Google Scholar 

  55. Esteller M, Corn PG, Baylin SB, Herman JG. Perspectives in Cancer Res a gene hypermethylation profile of human cancer 1. Cancer Res. 2001;61:3225–9.

    PubMed  CAS  Google Scholar 

  56. Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochem Biophys Acta. 2007;1775(1):138–62.

    PubMed  CAS  Google Scholar 

  57. Futscher BW, Oshiro MM, Wozniak RJ, et al. Role for DNA methylation in the control of cell type–specific maspin expression. Nat Genet. 2002;31(2):175–9.

    Article  PubMed  CAS  Google Scholar 

  58. Irizarry R, Ladd-Acosta C, Wen B, et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009;41(2):178–86.

    Article  PubMed  CAS  Google Scholar 

  59. Feinberg P. Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res. 1999;59(7 Suppl):1743s–6s.

    PubMed  CAS  Google Scholar 

  60. Holm TM, Jackson-Grusby L, Brambrink T, et al. Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer cell. 2005;8(4):275–85.

    Article  PubMed  CAS  Google Scholar 

  61. Ito Y, Koessler T, Ibrahim AEK, et al. Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer. Hum Mol Genet. 2008;17(17):2633–43.

    Article  PubMed  CAS  Google Scholar 

  62. Greger V, Passarge E, Höpping W, Messmer E, Horsthemke B. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet. 1989;83(2):155–8.

    Article  PubMed  CAS  Google Scholar 

  63. Wong J, Barrett T, Emond J, Reid J. Promoter is hypermethylated adenocarcinomas at a high frequency in esophageal. Cancer Res. 1997;57:2619–22.

    PubMed  CAS  Google Scholar 

  64. Belinsky S, Nikula KJ, Palmisano W, et al. Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA. 1998;95(20):11891–6.

    Article  PubMed  CAS  Google Scholar 

  65. Belinsky S. Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev Cancer. 2004;4(9):707–17.

    Article  PubMed  CAS  Google Scholar 

  66. Barletta JM, Rainier S, Feinberg P. Reversal of loss of imprinting in tumor cells by 5-aza-2′-deoxycytidine. Cancer Res. 1997;57(1):48–50.

    PubMed  CAS  Google Scholar 

  67. Murrell A. Genomic imprinting and cancer: from primordial germ cells to somatic cells. Sci World J. 2006;6:1888–910.

    Google Scholar 

  68. Costello JF, Frühwald MC, Smiraglia DJ, et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000;24(2):132–8.

    Article  PubMed  CAS  Google Scholar 

  69. Adorján P. Tumour class prediction and discovery by microarray-based DNA methylation analysis. Nucleic Acids Res. 2002;30(5):e21.

    Article  PubMed  Google Scholar 

  70. Ehrich M, Turner J, Gibbs P, et al. Cytosine methylation profiling of cancer cell lines. Proc Natl Acad Sci USA. 2008;105(12):4844–9.

    Article  PubMed  CAS  Google Scholar 

  71. Toyota M. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999;96(15):8681–6.

    Article  PubMed  CAS  Google Scholar 

  72. Shen L, Toyota M, Kondo Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci USA. 2007;104(47):18654–9.

    Article  PubMed  CAS  Google Scholar 

  73. Roman-Gomez J, Jimenez-Velasco A, Agirre X, et al. Lack of CpG island methylator phenotype defines a clinical subtype of T-cell acute lymphoblastic leukemia associated with good prognosis. J Clin Oncol. 2005;23(28):7043–9.

    Article  PubMed  CAS  Google Scholar 

  74. Kuang S-Q, Tong W-G, Yang H, et al. Genome-wide identification of aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia. Leukemia. 2008;22(8):1529–38.

    Article  PubMed  CAS  Google Scholar 

  75. J-pierre I. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004;4(December):988–93.

    Google Scholar 

  76. Doi A, Park I-H, Wen B, et al. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009;41(12):1350–3.

    Article  PubMed  CAS  Google Scholar 

  77. Sawan C, Vaissière T, Murr R, Herceg Z. Epigenetic drivers and genetic passengers on the road to cancer. Mutat Res. 2008;642(1–2):1–13.

    PubMed  CAS  Google Scholar 

  78. Milani L, Lundmark A, Kiialainen A, et al. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia. Blood. 2010;115(6):1214–25.

    Article  PubMed  CAS  Google Scholar 

  79. Bennett LB, Schnabel JL, Kelchen JM, et al. DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma. Genes Chromosom Cancer. 2010;48(9):828–41.

    Article  CAS  Google Scholar 

  80. O’Riain C. UKPMC Funders Group Array-based DNA methylation profiling in follicular lymphoma. Leukemia. 2010;23(10):1858–66.

    Article  CAS  Google Scholar 

  81. Figueroa ME, Wouters BJ, Skrabanek L, et al. Genome-wide epigenetic analysis delineates a biologically ­distinct immature acute leukemia with myeloid/T-lymphoid features. Blood. 2009;113(12):2795–804.

    Article  PubMed  CAS  Google Scholar 

  82. Figueroa ME, Lugthart S, Li Y, et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 2010;17(1):13–27.

    Article  PubMed  CAS  Google Scholar 

  83. Cheung HH, Lee TL, Davis AJ, et al. Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer. Br J Cancer. 2010;102(2):419–27.

    Article  PubMed  CAS  Google Scholar 

  84. Alaminos M, Davalos V, Cheung N-KV, Gerald WL, Esteller M. Clustering of gene hypermethylation associated with clinical risk groups in neuroblastoma. J Nat Cancer Inst. 2004;96(16):1208–19.

    Article  PubMed  CAS  Google Scholar 

  85. Marsit CJ, Christensen BC, Houseman EA, et al. Epigenetic profiling reveals etiologically distinct patterns of DNA methylation in head and neck squamous cell carcinoma. Carcinogen. 2009;30(3):416–22.

    Article  CAS  Google Scholar 

  86. Martinez R, Martin-Subero JI, Rohde V, et al. A microarray-based DNA methylation study of glioblastoma multiforme. Epigenetics. 2009;4(4):255–64.

    PubMed  CAS  Google Scholar 

  87. Wu X, Rauch T, Zhong X, et al. CpG island hypermethylation in human astrocytomas. Cancer Res. 2010;70(7):2718–27.

    Article  PubMed  CAS  Google Scholar 

  88. Varier R, Timmers HTM. Histone lysine methylation and demethylation pathways in cancer. Biochem Biophys Acta. 2011;1815:75–89.

    PubMed  CAS  Google Scholar 

  89. Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37(4):391–400.

    Article  PubMed  CAS  Google Scholar 

  90. Seligson DB, Horvath S, Shi T, et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature. 2005;435(7046):1262–6.

    Article  PubMed  CAS  Google Scholar 

  91. Ellinger J, Kahl P, Mertens C, et al. Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int J Cancer. 2010;127(10):2360–6.

    Article  PubMed  CAS  Google Scholar 

  92. Manuyakorn A, Paulus R, Farrell J, Dawson NA, Tze S, Cheung-Lau G, et al. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J Clin Oncol. 2010;28(8):1358–65.

    Article  PubMed  CAS  Google Scholar 

  93. Elsheikh SE, Green AR, Rakha EA, et al. Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res. 2009;69(9):3802–9.

    Article  PubMed  CAS  Google Scholar 

  94. Ellinger J, Kahl P, von der Gathen J, et al. Global levels of histone modifications predict prostate cancer recurrence. Prostate. 2010;70(1):61–9.

    Article  PubMed  CAS  Google Scholar 

  95. Bianco-Miotto T, Chiam K, Buchanan G, et al. Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol Biomarkers Prev. 2010;19(10):2611–22.

    Article  PubMed  CAS  Google Scholar 

  96. Wei Y, Xia W, Zhang Z, et al. Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Mol Carcinog. 2008;47(9):701–6.

    Article  PubMed  CAS  Google Scholar 

  97. Berezovska OP, Glinskii AB, Yang Z, et al. Essential role for activation of the Polycomb group (PcG) protein chromatin silencing pathway in metastatic prostate cancer. Cell Cycle. 2006;5(16):1886–901.

    Article  PubMed  CAS  Google Scholar 

  98. Mosashvilli D, Kahl P, Mertens C, et al. Global histone acetylation levels: prognostic relevance in patients with renal cell carcinoma. Cancer Sci. 2010;101(12):2664–9. doi:10.1111/j.1349-7006.2010.01717.x. Epub 2010 Sep 1.

    Article  PubMed  CAS  Google Scholar 

  99. I H, Ko E, Kim Y, et al. Association of global levels of histone modifications with recurrence-free survival in stage IIB and III esophageal squamous cell carcinomas. Cancer Epidemiol Biomarkers Prev. 2010;19(2):566–73.

    Google Scholar 

  100. Sporn JC, Kustatscher G, Hothorn T, et al. Histone macroH2A isoforms predict the risk of lung cancer ­recurrence. Oncogene. 2009;28(38):3423–8.

    Article  PubMed  CAS  Google Scholar 

  101. Mikesch J-H, Gronemeyer H, So CWE. Discovery of novel transcriptional and epigenetic targets in APL by global ChIP analyses: emerging opportunity and challenge. Cancer Cell. 2010;17(2):112–4.

    Article  PubMed  CAS  Google Scholar 

  102. Boukarabila H, Saurin AJ, Batsché E, et al. The PRC1 Polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation. Genes Dev. 2009;23(10):1195–206.

    Article  PubMed  CAS  Google Scholar 

  103. Krivtsov AV, Armstrong SA. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer. 2007;7(11):823–33.

    Article  PubMed  CAS  Google Scholar 

  104. Guenther MG, Lawton LN, Rozovskaia T, et al. Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia. Genes Dev. 2008;22(24):3403–8.

    Article  PubMed  CAS  Google Scholar 

  105. Krivtsov AV, Feng Z, Lemieux ME, et al. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008;14(5):355–68.

    Article  PubMed  CAS  Google Scholar 

  106. Xu S, Powers M. Nuclear pore proteins and cancer. Semin Cell Dev Biol. 2009;20(5):620–30.

    Article  PubMed  CAS  Google Scholar 

  107. Wang GG, Cai L, Pasillas MP, Kamps MP. NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol. 2007;9(7):804–12.

    Article  PubMed  CAS  Google Scholar 

  108. Wang GG, Song J, Wang Z, et al. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature. 2009;459(7248):847–51.

    Article  PubMed  CAS  Google Scholar 

  109. Figueroa ME, Reimers M, Thompson RF, et al. An integrative genomic and epigenomic approach for the study of transcriptional regulation. PloS One. 2008;3(3):e1882.

    Article  PubMed  CAS  Google Scholar 

  110. Sauvageau M, Sauvageau G. Polycomb group genes: keeping stem cell activity in balance. PLoS Biol. 2008;6(4):e113.

    Article  PubMed  CAS  Google Scholar 

  111. Zhang L, Zhong K, Dai Y, Zhou H. Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients. J Gastroenterol. 2009;44(4):305–12.

    Article  PubMed  CAS  Google Scholar 

  112. Yu J, Yu J, Rhodes DR, et al. A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res. 2007;67(22):10657–63.

    Article  PubMed  CAS  Google Scholar 

  113. Yu J, Cao Q, Mehra R, et al. Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell. 2007;12(5):419–31.

    Article  PubMed  CAS  Google Scholar 

  114. Kondo Y, Shen L, Cheng AS, et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nat Genet. 2008;40(6):741–50.

    Article  PubMed  CAS  Google Scholar 

  115. Ke X-S, Qu Y, Rostad K, et al. Genome-wide profiling of histone h3 lysine 4 and lysine 27 trimethylation reveals an epigenetic signature in prostate. Carcinogen. PloS One. 2009;4(3):e4687.

    Article  PubMed  CAS  Google Scholar 

  116. Viré E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439(7078):871–4.

    Article  PubMed  CAS  Google Scholar 

  117. Widschwendter M, Fiegl H, Egle D, et al. Epigenetic stem cell signature in cancer. Nat Genet. 2007;39(2):157–8.

    Article  PubMed  CAS  Google Scholar 

  118. Schlesinger Y, Straussman R, Keshet I, 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  PubMed  CAS  Google Scholar 

  119. Li M, Chen W-D, Papadopoulos N, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009;27(9):858–63.

    Article  PubMed  CAS  Google Scholar 

  120. Fanelli M, Amatori S, Barozzi I, et al. Pathology tissue-chromatin immunoprecipitation, coupled with high-throughput sequencing, allows the epigenetic profiling of patient samples. Proc Natl Acad Sci USA. 2010;107(50):21535–40.

    Article  PubMed  CAS  Google Scholar 

  121. Gupta R, Nagarajan A, Wajapeyee N. Advances in genome-wide DNA methylation analysis. BioTechniques. 2010;49(4):iii–xi.

    Google Scholar 

  122. Andersen JB, Factor VM, Marquardt JU, et al. An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer. Sci Transl Med. 2010;2(54):54ra77.

    Google Scholar 

  123. Du Z, Song J, Wang Y, et al. DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination. Sci Signal. 2010;3(146):ra80.

    Google Scholar 

  124. Lin YH, Kakadia PM, Chen Y, et al. Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias. Blood. 2009;114(3):651–658.

    Google Scholar 

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Acknowledgements

Work in the PF laboratory is supported by institutional grants from Inserm and the CNRS, and by specific grants from the “Fondation Princesse Grace de Monaco”, the “Association pour la Recherche sur le Cancer” (ARC), the “Agence Nationale de la Recherche” (ANR), the “Institut National du Cancer” (INCa) and the Commission of the European Communities. We extend our acknowledgements to Pierre Cauchy for critical proofreading of the manuscript. AP was supported by a Marie Curie research training fellowship (MRTN-CT-2006-035733) and is now supported by the “Fondation pour la Recherche Medicale” (FRM). JJ was supported by the “Fondation Franco-Chinoise pour la Science et ses Applications”, the China Scholarship Council and Marseille-Nice Genopole.

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Authors and Affiliations

  1. Centre d’Immunologie de Marseille-Luminy, Université Aix-Marseille, Marseille, France

    Aleksandra Pekowska PhD, Joaquin Zacarias-Cabeza PhD, Jinsong Jia MD, PhD, Pierre Ferrier PhD & Salvatore Spicuglia PhD

  2. CNRS, UMR6102, Marseille, France

    Aleksandra Pekowska PhD, Joaquin Zacarias-Cabeza PhD, Jinsong Jia MD, PhD, Pierre Ferrier PhD & Salvatore Spicuglia PhD

  3. Inserm, U631, Marseille, France

    Aleksandra Pekowska PhD, Joaquin Zacarias-Cabeza PhD, Jinsong Jia MD, PhD, Pierre Ferrier PhD & Salvatore Spicuglia PhD

  4. Institute of Hematology, People’s Hospital, Beijing University, Beijing, People’s Republic of China

    Jinsong Jia MD, PhD

Authors
  1. Aleksandra Pekowska PhD
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  2. Joaquin Zacarias-Cabeza PhD
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  3. Jinsong Jia MD, PhD
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  4. Pierre Ferrier PhD
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  5. Salvatore Spicuglia PhD
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Corresponding author

Correspondence to Salvatore Spicuglia PhD .

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Editors and Affiliations

  1. Department of Surgical and, Oncological Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  2. , National Consortium for Research on, University D’Annunzio, Via dei Vestini 31, Chieti, 66013, Italy

    Stefano Iacobelli

  3. INSERM U624, av. de Luminy 163, Marseille, 13288, France

    Juan Iovanna

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Pekowska, A., Zacarias-Cabeza, J., Jia, J., Ferrier, P., Spicuglia, S. (2012). The Role of Epigenetics in Cancer: From Molecular Function to High-Throughput Assays. In: Russo, A., Iacobelli, S., Iovanna, J. (eds) Diagnostic, Prognostic and Therapeutic Value of Gene Signatures. Current Clinical Pathology. Humana Press. https://doi.org/10.1007/978-1-61779-358-5_9

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  • DOI: https://doi.org/10.1007/978-1-61779-358-5_9

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