Human Genetics

, Volume 133, Issue 6, pp 713–725 | Cite as

Cancer genomics identifies disrupted epigenetic genes

Review Paper

Abstract

Latest advances in genome technologies have greatly advanced the discovery of epigenetic genes altered in cancer. The initial single candidate gene approaches have been coupled with newly developed epigenomic platforms to hasten the convergence of scientific discoveries and translational applications. Here, we present an overview of the evolution of cancer epigenomics and an updated catalog of disruptions in epigenetic pathways, whose misregulation can culminate in cancer. The creation of these basic mutational catalogs in cell lines and primary tumors will provide us with enough knowledge to move diagnostics and therapy from the laboratory bench to the bedside.

References

  1. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837PubMedGoogle Scholar
  2. Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M, Kouzarides T (2010) Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 143:470–484PubMedCentralPubMedGoogle Scholar
  3. Berdasco M, Ropero S, Setien F, Fraga MF, Lapunzina P, Losson R, Alaminos M, Cheung NK, Rahman N, Esteller M (2009) Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci USA 106:21830–21835PubMedCentralPubMedGoogle Scholar
  4. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A (2009) An operational definition of epigenetics. Genes Dev 23:781–783PubMedCentralPubMedGoogle Scholar
  5. Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ 3rd, Gingeras TR, Schreiber SL, Lander ES (2005) Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169–181PubMedGoogle Scholar
  6. Bhattacharyya S, Yu Y, Suzuki M, Campbell N, Mazdo J, Vasanthakumar A, Bhagat TD, Nischal S, Christopeit M, Parekh S, Steidl U, Godley L, Maitra A, Greally JM, Verma A (2013) Genome-wide hydroxymethylation tested using the HELP-GT assay shows redistribution in cancer. Nucleic Acids Res. doi:10.1093/nar/gkt601 Google Scholar
  7. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21PubMedGoogle Scholar
  8. Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784PubMedGoogle Scholar
  9. Byrd JC, Marcucci G, Parthun MR, Xiao JJ, Klisovic RB, Moran M, Lin TS, Liu S, Sklenar AR, Davis ME, Lucas DM, Fischer B, Shank R, Tejaswi SL, Binkley P, Wright J, Chan KK, Grever MR (2005) A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 105:959–967PubMedGoogle Scholar
  10. Ceol CJ, Houvras Y, Jane-Valbuena J, Bilodeau S, Orlando DA, Battisti V, Fritsch L, Lin WM, Hollmann TJ, Ferre F, Bourque C, Burke CJ, Turner L, Uong A, Johnson LA, Beroukhim R, Mermel CH, Loda M, Ait-Si-Ali S, Garraway LA, Young RA, Zon LI (2011) The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature 471:513–517PubMedCentralPubMedGoogle Scholar
  11. Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, Thompson RC, Muller S, Knapp S, Wang J (2013) Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res 19:1748–1759PubMedGoogle Scholar
  12. Chin L, Andersen JN, Futreal PA (2011) Cancer genomics: from discovery science to personalized medicine. Nat Med 17:297–303PubMedGoogle Scholar
  13. Christians A, Hartmann C, Benner A, Meyer J, von Deimling A, Weller M, Wick W, Weiler M (2012) Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma. PLoS One 7:e33449PubMedCentralPubMedGoogle Scholar
  14. Clapier CR, Cairns BR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78:273–304PubMedGoogle Scholar
  15. Clark SJ, Harrison J, Paul CL, Frommer M (1994) High sensitivity mapping of methylated cytosines. Nucleic Acids Res 22:2990–2997PubMedCentralPubMedGoogle Scholar
  16. Cohen I, Poręba E, Kamieniarz K, Schneider R (2011) Histone modifiers in cancer: friends or foes? Genes Cancer 2(6):631–647PubMedCentralPubMedGoogle Scholar
  17. Coles AH, Jones SN (2009) The ING gene family in the regulation of cell growth and tumorigenesis. J Cell Physiol 218:45–57PubMedCentralPubMedGoogle Scholar
  18. Cornen S, Adelaide J, Bertucci F, Finetti P, Guille A, Birnbaum DJ, Birnbaum D, Chaffanet M (2012) Mutations and deletions of ARID1A in breast tumors. Oncogene 31:4255–4256PubMedGoogle Scholar
  19. Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomaki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Su Huang H, Petrelli NJ, Zhang X, O’Dorisio MS, Held WA, Cavenee WK, Plass C (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24:132–138PubMedGoogle Scholar
  20. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714PubMedCentralPubMedGoogle Scholar
  21. Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150:12–27PubMedGoogle Scholar
  22. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lecluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguie F, Fontenay M, Vainchenker W, Bernard OA (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 360:2289–2301PubMedGoogle Scholar
  23. 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:E32PubMedCentralPubMedGoogle Scholar
  24. Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298PubMedGoogle Scholar
  25. Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159PubMedGoogle Scholar
  26. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12:861–874PubMedGoogle Scholar
  27. Esteller M, Almouzni G (2005) How epigenetics integrates nuclear functions. Workshop on epigenetics and chromatin: transcriptional regulation and beyond. EMBO Rep 6:624–628PubMedCentralPubMedGoogle Scholar
  28. Fabbri M, Calore F, Paone A, Galli R, Calin GA (2013) Epigenetic regulation of miRNAs in cancer. Adv Exp Med Biol 754:137–148PubMedGoogle Scholar
  29. Farnham PJ (2009) Insights from genomic profiling of transcription factors. Nat Rev Genet 10:605–616PubMedCentralPubMedGoogle Scholar
  30. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153PubMedGoogle Scholar
  31. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE (2010) Selective inhibition of BET bromodomains. Nature 468:1067–1073PubMedCentralPubMedGoogle Scholar
  32. Fraga MF, Esteller M (2002) DNA methylation: a profile of methods and applications. Biotechniques 33:632,634,636–49Google Scholar
  33. Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Perez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37:391–400PubMedGoogle Scholar
  34. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105PubMedCentralPubMedGoogle Scholar
  35. Frigola J, Ribas M, Risques RA, Peinado MA (2002) Methylome profiling of cancer cells by amplification of inter-methylated sites (AIMS). Nucleic Acids Res 30:e28PubMedCentralPubMedGoogle Scholar
  36. Gao X, Huang M, Liu L, He Y, Yu Q, Zhao H, Zhou C, Zhang J, Zhu Z, Wan J, Jiang X, Gao Y (2013) Insertion/deletion polymorphisms in the promoter region of BRM contribute to risk of hepatocellular carcinoma in Chinese populations. PLoS One 8:e55169PubMedCentralPubMedGoogle Scholar
  37. Garcia JS, Jain N, Godley LA (2010) An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes. Oncol Target Ther 3:1–13Google Scholar
  38. Garraway LA, Lander ES (2013) Lessons from the cancer genome. Cell 153:17–37PubMedGoogle Scholar
  39. Gorrini C, Squatrito M, Luise C, Syed N, Perna D, Wark L, Martinato F, Sardella D, Verrecchia A, Bennett S, Confalonieri S, Cesaroni M, Marchesi F, Gasco M, Scanziani E, Capra M, Mai S, Nuciforo P, Crook T, Lough J, Amati B (2007) Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature 448:1063–1067PubMedGoogle Scholar
  40. Guil S, Soler M, Portela A, Carrere J, Fonalleras E, Gomez A, Villanueva A, Esteller M (2012) Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nat Struct Mol Biol 19:664–670PubMedGoogle Scholar
  41. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076PubMedCentralPubMedGoogle Scholar
  42. Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y (2004) SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 6:731–740PubMedGoogle Scholar
  43. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:9971003Google Scholar
  44. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311–318PubMedGoogle Scholar
  45. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCentralPubMedGoogle Scholar
  46. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Puca AA, Sayols S, Pujana MA, Serra-Musach J, Iglesias-Platas I, Formiga F, Fernandez AF, Fraga MF, Heath SC, Valencia A, Gut IG, Wang J, Esteller M (2012) Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA 109:10522–10527PubMedCentralPubMedGoogle Scholar
  47. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ (2009) DICER1 mutations in familial pleuropulmonary blastoma. Science 325:965PubMedCentralPubMedGoogle Scholar
  48. Huang TH, Perry MR, Laux DE (1999) Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet 8:459–470PubMedGoogle Scholar
  49. Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N, Rowan R, Amaral S, Curley D, Williams IR, Akashi K, Gilliland DG (2004) MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6:587–596PubMedGoogle Scholar
  50. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansen S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Janne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150:1107–1120PubMedCentralPubMedGoogle Scholar
  51. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Menard S, Croce CM (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67:8699–8707PubMedGoogle Scholar
  52. Jackson EM, Sievert AJ, Gai X, Hakonarson H, Judkins AR, Tooke L, Perin JC, Xie H, Shaikh TH, Biegel JA (2009) Genomic analysis using high-density single nucleotide polymorphism-based oligonucleotide arrays and multiplex ligation-dependent probe amplification provides a comprehensive analysis of INI1/SMARCB1 in malignant rhabdoid tumors. Clin Cancer Res 15:1923–1930PubMedCentralPubMedGoogle Scholar
  53. Johnson DS, Mortazavi A, Myers RM, Wold B (2007) Genome-wide mapping of in vivo protein-DNA interactions. Science 316:1497–1502PubMedGoogle Scholar
  54. Jones JS, Amos CI, Pande M, Gu X, Chen J, Campos IM, Wei Q, Rodriguez-Bigas M, Lynch PM, Frazier ML (2006) DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset. Cancer Epidemiol Biomarkers Prev 15:886–891PubMedGoogle Scholar
  55. Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K, Roden R, Glas R, Slamon D, Diaz LA Jr, Vogelstein B, Kinzler KW, Velculescu VE, Papadopoulos N (2010) Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330:228–231PubMedCentralPubMedGoogle Scholar
  56. Kaneda A, Feinberg AP (2005) Loss of imprinting of IGF2: a common epigenetic modifier of intestinal tumor risk. Cancer Res 65:11236–11240PubMedGoogle Scholar
  57. Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31:89–97PubMedGoogle Scholar
  58. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30:1956–1962PubMedCentralPubMedGoogle Scholar
  59. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705PubMedGoogle Scholar
  60. Krivtsov AV, Armstrong SA (2007) MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 7:823–833PubMedGoogle Scholar
  61. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921PubMedGoogle Scholar
  62. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens-Linders E, van Hoogen P, van Kessel AG, Raymakers RA, Kamping EJ, Verhoef GE, Verburgh E, Hagemeijer A, Vandenberghe P, de Witte T, van der Reijden BA, Jansen JH (2009) Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 41:838–842PubMedGoogle Scholar
  63. Lee JS, Smith E, Shilatifard A (2010) The language of histone crosstalk. Cell 142:682–685PubMedCentralPubMedGoogle Scholar
  64. Lehmann U, Hasemeier B, Christgen M, Muller M, Romermann D, Langer F, Kreipe H (2008) Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol 214:17–24PubMedGoogle Scholar
  65. Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, Kandoth C, Payton JE, Baty J, Welch J, Harris CC, Lichti CF, Townsend RR, Fulton RS, Dooling DJ, Koboldt DC, Schmidt H, Zhang Q, Osborne JR, Lin L, O’Laughlin M, McMichael JF, Delehaunty KD, McGrath SD, Fulton LA, Magrini VJ, Vickery TL, Hundal J, Cook LL, Conyers JJ, Swift GW, Reed JP, Alldredge PA, Wylie T, Walker J, Kalicki J, Watson MA, Heath S, Shannon WD, Varghese N, Nagarajan R, Westervelt P, Tomasson MH, Link DC, Graubert TA, DiPersio JF, Mardis ER, Wilson RK (2010) DNMT3A mutations in acute myeloid leukemia. N Engl J Med 363:2424–2433PubMedCentralPubMedGoogle Scholar
  66. Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926PubMedGoogle Scholar
  67. Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719PubMedGoogle Scholar
  68. Liang H, Cheung LW, Li J, Ju Z, Yu S, Stemke-Hale K, Dogruluk T, Lu Y, Liu X, Gu C, Guo W, Scherer SE, Carter H, Westin SN, Dyer MD, Verhaak RG, Zhang F, Karchin R, Liu CG, Lu KH, Broaddus RR, Scott KL, Hennessy BT, Mills GB (2012) Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer. Genome Res 22:2120–2129PubMedCentralPubMedGoogle Scholar
  69. Lin H, Wong RP, Martinka M, Li G (2009) Loss of SNF5 expression correlates with poor patient survival in melanoma. Clin Cancer Res 15:6404–6411PubMedGoogle Scholar
  70. Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR (2003) TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia 17:637–641PubMedGoogle Scholar
  71. Mar BG, Bullinger L, Basu E, Schlis K, Silverman LB, Dohner K, Armstrong SA (2012) Sequencing histone-modifying enzymes identifies UTX mutations in acute lymphoblastic leukemia. Leukemia 26:1881–1883PubMedGoogle Scholar
  72. Margueron R, Reinberg D (2011) The polycomb complex PRC2 and its mark in life. Nature 469:343–349PubMedCentralPubMedGoogle Scholar
  73. Matsubara D, Kishaba Y, Ishikawa S, Sakatani T, Oguni S, Tamura T, Hoshino H, Sugiyama Y, Endo S, Murakami Y, Aburatani H, Fukayama M, Niki T (2013) Lung cancer with loss of BRG1/BRM, shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features. Cancer Sci 104:266–273PubMedGoogle Scholar
  74. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA, Rossi S, Fernandez AF, Carneiro F, Oliveira C, Ferreira B, Liu CG, Villanueva A, Capella G, Schwartz S Jr, Shiekhattar R, Esteller M (2009) A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet 41:365–370PubMedGoogle Scholar
  75. Melo SA, Moutinho C, Ropero S, Calin GA, Rossi S, Spizzo R, Fernandez AF, Davalos V, Villanueva A, Montoya G, Yamamoto H, Schwartz S Jr, Esteller M (2010) A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 18:303–315PubMedGoogle Scholar
  76. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, Shashkin P, Charlot JF, Tcherpakov M, Corbett R, Tam A, Varhol R, Smailus D, Moksa M, Zhao Y, Delaney A, Qian H, Birol I, Schein J, Moore R, Holt R, Horsman DE, Connors JM, Jones S, Aparicio S, Hirst M, Gascoyne RD, Marra MA (2010) Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 42:181–185PubMedCentralPubMedGoogle Scholar
  77. Mosammaparast N, Shi Y (2010) Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu Rev Biochem 79:155–179PubMedGoogle Scholar
  78. Niu X, Zhang T, Liao L, Zhou L, Lindner DJ, Zhou M, Rini B, Yan Q, Yang H (2012) The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C. Oncogene 31:776–786PubMedGoogle Scholar
  79. O’Connor OA, Heaney ML, Schwartz L, Richardson S, Willim R, MacGregor-Cortelli B, Curly T, Moskowitz C, Portlock C, Horwitz S, Zelenetz AD, Frankel S, Richon V, Marks P, Kelly WK (2006) Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. J Clin Oncol 24:166–173PubMedGoogle Scholar
  80. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257PubMedGoogle Scholar
  81. O’Neill LP, Turner BM (2003) Immunoprecipitation of native chromatin: NChIP. Methods 31:76–82PubMedGoogle Scholar
  82. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, Gerhard DS, Fults DW, VandenBerg S, Berger MS, Marie SK, Shinjo SM, Clara C, Phillips PC, Minturn JE, Biegel JA, Judkins AR, Resnick AC, Storm PB, Curran T, He Y, Rasheed BA, Friedman HS, Keir ST, McLendon R, Northcott PA, Taylor MD, Burger PC, Riggins GJ, Karchin R, Parmigiani G, Bigner DD, Yan H, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE (2011) The genetic landscape of the childhood cancer medulloblastoma. Science 331:435–439PubMedCentralPubMedGoogle Scholar
  83. Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, Rossi D, Chadburn A, Murty VV, Mullighan CG, Gaidano G, Rabadan R, Brindle PK, Dalla-Favera R (2011) Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 471:189–195PubMedCentralPubMedGoogle Scholar
  84. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, Levine RL (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366:1079–1089PubMedCentralPubMedGoogle Scholar
  85. Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH, Zain J, Prince HM, Leonard JP, Geskin LJ, Reeder C, Joske D, Figg WD, Gardner ER, Steinberg SM, Jaffe ES, Stetler-Stevenson M, Lade S, Fojo AT, Bates SE (2009) Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27:5410–5417PubMedCentralPubMedGoogle Scholar
  86. Rando OJ, Chang HY (2009) Genome-wide views of chromatin structure. Annu Rev Biochem 78:245–271PubMedCentralPubMedGoogle Scholar
  87. Reik W, Lewis A (2005) Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet 6:403–410PubMedGoogle Scholar
  88. Rodriguez-Nieto S, Canada A, Pros E, Pinto AI, Torres-Lanzas J, Lopez-Rios F, Sanchez-Verde L, Pisano DG, Sanchez-Cespedes M (2011) Massive parallel DNA pyrosequencing analysis of the tumor suppressor BRG1/SMARCA4 in lung primary tumors. Hum Mutat 32:E1999–E2017PubMedGoogle Scholar
  89. Rodriguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17:330–339PubMedGoogle Scholar
  90. Rodriguez-Paredes M, Martinez de Paz A, Simó-Riudalbas L, Sayols S, Moutinho C, Moran S, Villanueva A, Vázquez-Cedeira M, Lazo PA, Carneiro F, Moura CS, Vieira J, Teixeira MR, Esteller M (2013) Gene amplification of the histone methyltransferase SETDB1 contributes to human lung tumorigenesis. Oncogene. doi:10.1038/onc.2013.239
  91. Ropero S, Fraga MF, Ballestar E, Hamelin R, Yamamoto H, Boix-Chornet M, Caballero R, Alaminos M, Setien F, Paz MF, Herranz M, Palacios J, Arango D, Orntoft TF, Aaltonen LA, Schwartz S Jr, Esteller M (2006) A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nat Genet 38:566–569PubMedGoogle Scholar
  92. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9:435–443PubMedGoogle Scholar
  93. Saunders LR, Verdin E (2007) Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene 26:5489–5504PubMedGoogle Scholar
  94. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tonjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jager N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Fruhwald MC, Roggendorf W, Kramm C, Durken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231PubMedGoogle Scholar
  95. Segal E, Widom J (2009) From DNA sequence to transcriptional behaviour: a quantitative approach. Nat Rev Genet 10:443–456PubMedCentralPubMedGoogle Scholar
  96. Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK (2005) Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435:1262–1266PubMedGoogle Scholar
  97. Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q (2002) A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res 62:4992–4995PubMedGoogle Scholar
  98. Simo-Riudalbas L, Melo SA, Esteller M (2011) DNMT3B gene amplification predicts resistance to DNA demethylating drugs. Genes Chromosom Cancer 50:527–534PubMedGoogle Scholar
  99. Sneeringer CJ, Scott MP, Kuntz KW, Knutson SK, Pollock RM, Richon VM, Copeland RA (2010) Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc Natl Acad Sci USA 107:20980–20985PubMedCentralPubMedGoogle Scholar
  100. Stunnenberg HG, Vermeulen M (2011) Towards cracking the epigenetic code using a combination of high-throughput epigenomics and quantitative mass spectrometry-based proteomics. BioEssays 33:547–551PubMedGoogle Scholar
  101. Taniguchi H, Jacinto FV, Villanueva A, Fernandez AF, Yamamoto H, Carmona FJ, Puertas S, Marquez VE, Shinomura Y, Imai K, Esteller M (2012) Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer. Oncogene 31:1988–1994PubMedCentralPubMedGoogle Scholar
  102. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, Tokino T (2008) Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res 68:4123–4132PubMedGoogle Scholar
  103. Uhlmann K, Brinckmann A, Toliat MR, Ritter H, Nurnberg P (2002) Evaluation of a potential epigenetic biomarker by quantitative methyl-single nucleotide polymorphism analysis. Electrophoresis 23:4072–4079PubMedGoogle Scholar
  104. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA (2011) Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469:539–542PubMedCentralPubMedGoogle Scholar
  105. Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318:1931–1934PubMedGoogle Scholar
  106. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C et al (2001) The sequence of the human genome. Science 291:1304–1351PubMedGoogle Scholar
  107. Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394:203–206PubMedGoogle Scholar
  108. Waddington CH (1942) The epigenotype. Endeavour 1:18–20Google Scholar
  109. Walsh CP, Chaillet JR, Bestor TH (1998) Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet 20:116–117PubMedGoogle Scholar
  110. Wang J, Iwasaki H, Krivtsov A, Febbo PG, Thorner AR, Ernst P, Anastasiadou E, Kutok JL, Kogan SC, Zinkel SS, Fisher JK, Hess JL, Golub TR, Armstrong SA, Akashi K, Korsmeyer SJ (2005) Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J 24:368–381PubMedCentralPubMedGoogle Scholar
  111. Wang GG, Cai L, Pasillas MP, Kamps MP (2007) NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol 9:804–812PubMedGoogle Scholar
  112. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40:897–903PubMedCentralPubMedGoogle Scholar
  113. Wang JR, Gramling SJ, Goldstein DP, Cheng D, Chen D, Azad AK, Tse A, Hon H, Chen Z, Mirshams M, Simpson C, Huang SH, Marquez S, O’Sullivan B, Liu FF, Roberts H, Xu W, Brown DH, Gilbert RW, Gullane PJ, Irish JC, Reisman DN, Liu G (2013) Association of two BRM promoter polymorphisms with head and neck squamous cell carcinoma risk. CarcinogenesisGoogle Scholar
  114. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schubeler D (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37:853–862PubMedGoogle Scholar
  115. Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504PubMedCentralPubMedGoogle Scholar
  116. Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland AM, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH, Lees E (2000) BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Cancer Res 60:6171–6177PubMedGoogle Scholar
  117. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ (2012) St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome P, Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253PubMedCentralPubMedGoogle Scholar
  118. Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T, Memeo L, Hibshoosh H, Parsons R (2008) BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer Res 68:1667–1674PubMedCentralPubMedGoogle Scholar
  119. Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, Creighton CJ, Dhanasekaran SM, Shen R, Chen G, Morris DS, Marquez VE, Shah RB, Ghosh D, Varambally S, Chinnaiyan AM (2007) Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell 12:419–431PubMedGoogle Scholar
  120. Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481:157–163PubMedCentralPubMedGoogle Scholar
  121. Zhang X, Sun Q, Shan M, Niu M, Liu T, Xia B, Liang X, Wei W, Sun S, Zhang Y, Liu XS, Song Q, Yang Y, Ma Y, Liu Y, Yang L, Ren Y, Zhang G, Pang D (2013) Promoter hypermethylation of ARID1A gene is responsible for its low mRNA expression in many invasive breast cancers. PLoS One 8:e53931PubMedCentralPubMedGoogle Scholar
  122. Zou X, Ma W, Solov’yov IA, Chipot C, Schulten K (2012) Recognition of methylated DNA through methyl-CpG binding domain proteins. Nucleic Acids Res 40(6):2747–2758PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Cancer Epigenetics and Biology Program (PEBC)Bellvitge Biomedical Research Institute (IDIBELL)BarcelonaSpain
  2. 2.Department of Physiological Sciences II, School of MedicineUniversity of BarcelonaBarcelonaSpain
  3. 3.Institució Catalana de Recerca i Estudis Avançats (ICREA)BarcelonaSpain

Personalised recommendations