Mutations in chromatin machinery and pediatric high-grade glioma

Science Advances

Volumn 2, Issue 3, 2016, Pages

  Lulla, Rishi R ^a   Saratsis, Amanda Muhs ^a   Hashizume, Rintaro ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHROMOSOMES; DISEASES; MACHINERY; PEDIATRICS;

BIOLOGICAL BEHAVIOR; BRAIN TUMORS; CENTRAL NERVOUS SYSTEMS; CHROMATIN REGULATION; DISEASE TREATMENT; HIGH-GRADE GLIOMAS; LOW-GRADE GLIOMAS; SURVIVAL RATE;

TUMORS;

CHROMATIN; HISTONE;

ANIMAL; BRAIN NEOPLASMS; CANCER GRADING; CELL TRANSFORMATION; CHROMATIN; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENE SILENCING; GENETIC EPIGENESIS; GENETICS; GLIOMA; HUMAN; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; PATHOLOGY; TRANSCRIPTION INITIATION;

ANIMALS; BRAIN NEOPLASMS; CELL TRANSFORMATION, NEOPLASTIC; CHROMATIN; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; GLIOMA; HISTONES; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM GRADING; TRANSCRIPTIONAL ACTIVATION;

EID: 84983762412     PISSN: None     EISSN: 23752548     Source Type: Journal    
DOI: 10.1126/sciadv.1501354     Document Type: Review

References (72)

1. D. Sturm, H. Witt, V. Hovestadt, D.-A. Khuong-Quang, D. T. W. Jones, C. Konermann, E. Pfaff, M. Tönjes, M. Sill, S. Bender, M. Kool, M. Zapatka, N. Becker, M. Zucknick, T. Hielscher, X.-Y. Liu, A. M. Fontebasso, M. Ryzhova, S. Albrecht, K. Jacob, M. Wolter, M. Ebinger, M. U. Schuhmann, T. van Meter, M. C. Frühwald, H. Hauch, A. Pekrun, B. Radlwimmer, T. Niehues, G. von Komorowski, M. Dürken, A. E. Kulozik, J. Madden, A. Donson, N. K. Foreman, R. Drissi, M. Fouladi, W. Scheurlen, A. von Deimling, C. Monoranu, W. Roggendorf, C. Herold-Mende, A. Unterberg, C. M. Kramm, J. Felsberg, C. Hartmann, B. Wiestler, W. Wick, T. Milde, O. Witt, A. M. Lindroth, J. Schwartzentruber, D. Faury, A. Fleming, M. Zakrzewska, P. P. Liberski, K. Zakrzewski, P. Hauser, M. Garami, A. Klekner, L. Bognar, S. Morrissy, F. Cavalli, M. D. Taylor, P. van Sluis, J. Koster, R. Versteeg, R. Volckmann, T. Mikkelsen, K. Aldape, G. Reifenberger, V. P. Collins, J. Majewski, A. Korshunov, P. Lichter, C. Plass, N. Jabado, S. M. Pfister, Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22, 425-437 (2012).
2. D. Sturm, S. Bender, D. T. W. Jones, P. Lichter, J. Grill, O. Becher, C. Hawkins, J. Majewski, C. Jones, J. F. Costello, A. Iavarone, K. Aldape, C. W. Brennan, N. Jabado, S. M. Pfister, Paediatric and adult glioblastoma: Multiform (epi)genomic culprits emerge. Nat. Rev. Cancer 14, 92-107 (2014).
3. S. S. Donaldson, F. Laningham, P. G. Fisher, Advances toward an understanding of brainstem gliomas. J. Clin. Oncol. 24, 1266-1272 (2006).
4. K. E. Warren, Diffuse intrinsic pontine glioma: Poised for progress. Front. Oncol. 2, 205 (2012).
5. N. J. Robison, M. W. Kieran, Diffuse intrinsic pontine glioma: A reassessment. J. Neurooncol. 119, 7-15 (2014).
6. D. E. Roos, J. G. Smith, Randomized trial on radiotherapy for paediatric diffuse intrinsic pontine glioma (DIPG). Radiother. Oncol. 113, 425 (2014).
7. H. P. Fontanilla, C. C. Pinnix, L. M. Ketonen, S. Y. Woo, T. S. Vats, M. E. Rytting, J. E. Wolff, A. Mahajan, Palliative reirradiation for progressive diffuse intrinsic pontine glioma. Am. J. Clin. Oncol. 35, 51-57 (2012).
8. A. J. Barkovich, J. Krischer, L. A. Kun, R. J. Packer, R. A. Zimmerman, C. R. Freeman, W. M. Wara, L. Albright, J. C. Allen, H. J. Hoffman, Brain stem gliomas: A classification system based on magnetic resonance imaging. Pediatr. Neurosurg. 16, 73-83 (1990).
9. H. S. Phillips, S. Kharbanda, R. Chen, W. F. Forrest, R. H. Soriano, T. D. Wu, A. Misra, J. M. Nigro, H. Colman, L. Soroceanu, P. M. Williams, Z. Modrusan, B. G. Feuerstein, K. Aldape, Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9, 157-173 (2006).
10. D.-A. Khuong-Quang, P. Buczkowicz, P. Rakopoulos, X.-Y. Liu, A. M. Fontebasso, E. Bouffet, U. Bartels, S. Albrecht, J. Schwartzentruber, L. Letourneau, M. Bourgey, G. Bourque, A. Montpetit, G. Bourret, P. Lepage, A. Fleming, P. Lichter, M. Kool, A. von Deimling, D. Sturm, A. Korshunov, D. Faury, D. T. Jones, J. Majewski, S. M. Pfister, N. Jabado, C. Hawkins, K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol. 124, 439-447 (2012).
11. J. Schwartzentruber, A. Korshunov, X.-Y. Liu, D. T. W. Jones, E. Pfaff, K. Jacob, D. Sturm, A. M. Fontebasso, D.-A. K. Quang, M. Tönjes, V. Hovestadt, S. Albrecht, M. Kool, A. Nantel, C. Konermann, A. Lindroth, N. Jäger, T. Rausch, M. Ryzhova, J. O. Korbel, T. Hielscher, P. Hauser, M. Garami, A. Klekner, L. Bognar, M. Ebinger, M. U. Schuhmann, W. Scheurlen, A. Pekrun, M. C. Frühwald, W. Roggendorf, C. Kramm, M. Dürken, J. Atkinson, P. Lepage, A. Montpetit, M. Zakrzewska, K. Zakrzewski, P. P. Liberski, Z. Dong, P. Siegel, A. E. Kulozik, M. Zapatka, A. Guha, D. Malkin, J. Felsberg, G. Reifenberger, A. von Deimling, K. Ichimura, V. P. Collins, H. Witt, T. Milde, O. Witt, C. Zhang, P. Castelo-Branco, P. Lichter, D. Faury, U. Tabori, C. Plass, J. Majewski, S. M. Pfister, N. Jabado, Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226-231 (2012).
12. G. Wu, A. Broniscer, T. A. McEachron, C. Lu, B. S. Paugh, J. Becksfort, C. Qu, L. Ding, R. Huether, M. Parker, J. Zhang, A. Gajjar, M. A. Dyer, C. G. Mullighan, R. J. Gilbertson, E. R. Mardis, R. K. Wilson, J. R. Downing, D. W. Ellison, J. Zhang, S. J. Baker; St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project, Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat. Genet. 44, 251-253 (2012).
13. S. Henikoff, Nucleosome destabilization in the epigenetic regulation of gene expression. Nat. Rev. Genet. 9, 15-26 (2008).
14. T. Roujeau, G. Machado, M. R. Garnett, C. Miquel, S. Puget, B. Geoerger, J. Grill, N. Boddaert, F. Di Rocco, M. Zerah, C. Sainte-Rose, Stereotactic biopsy of diffuse pontine lesions in children. J. Neurosurg. 107 (Suppl. 1), 1-4 (2007).
15. S. Puget, C. Philippe, D. A. Bax, B. Job, P. Varlet, M.-P. Junier, F. Andreiuolo, D. Carvalho, R. Reis, L. Guerrini-Rousseau, T. Roujeau, P. Dessen, C. Richon, V. Lazar, G. Le Teuff, C. Sainte-Rose, B. Geoerger, G. Vassal, C. Jones, J. Grill, Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PLOS One 7, e30313 (2012).
16. B. Geoerger, D. Hargrave, F. Thomas, A. Ndiaye, D. Frappaz, F. Andreiuolo, P. Varlet, I. Aerts, R. Riccardi, T. Jaspan, E. Chatelut, M.-C. Le Deley, X. Paoletti, C. Saint-Rose, P. Leblond, B. Morland, J.-C. Gentet, V. Méresse, G. Vassal; ITCC (Innovative Therapies for Children with Cancer) European Consortium, Innovative Therapies for Children with Cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors. Neuro Oncol. 13, 109-118 (2011).
17. A. M. Fontebasso, S. Papillon-Cavanagh, J. Schwartzentruber, H. Nikbakht, N. Gerges, P.-O. Fiset, D. Bechet, D. Faury, N. De Jay, L. A. Ramkissoon, A. Corcoran, D. T. W. Jones, D. Sturm, P. Johann, T. Tomita, S. Goldman, M. Nagib, A. Bendel, L. Goumnerova, D. C. Bowers, J. R. Leonard, J. B. Rubin, T. Alden, S. Browd, J. R. Geyer, S. Leary, G. Jallo, K. Cohen, N. Gupta, M. D. Prados, A.-S. Carret, B. Ellezam, L. Crevier, A. Klekner, L. Bognar, P. Hauser, M. Garami, J. Myseros, Z. Dong, P. M. Siegel, H. Malkin, A. H. Ligon, S. Albrecht, S. M. Pfister, K. L. Ligon, J. Majewski, N. Jabado, M. W. Kieran, Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat. Genet. 46, 462-466 (2014).
18. K. R. Taylor, A. Mackay, N. Truffaux, Y. S. Butterfield, O. Morozova, C. Philippe, D. Castel, C. S. Grasso, M. Vinci, D. Carvalho, A. M. Carcaboso, C. de Torres, O. Cruz, J. Mora, N. Entz-Werle, W. J. Ingram, M. Monje, D. Hargrave, A. N. Bullock, S. Puget, S. Yip, C. Jones, J. Grill, Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat. Genet. 46, 457-461 (2014).
19. D. A. Walker, J. Liu, M. Kieran, N. Jabado, S. Picton, R. Packer, C. St. Rose; CPN Paris 2011 Conference Consensus Group, A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol. 15, 462-468 (2013).
20. I. Maze, K.-M. Noh, C. D. Allis, Histone regulation in the CNS: Basic principles of epigenetic plasticity. Neuropsychopharmacology 38, 3-22 (2013).
21. S. J. Elsaesser, A. D. Goldberg, C. D. Allis, New functions for an old variant: No substitute for histone H3.3. Curr. Opin. Genet. Dev. 20, 110-117 (2010).
22. P. J. Skene, S. Henikoff, Histone variants in pluripotency and disease. Development 140, 2513-2524 (2013).
23. N. Mosammaparast, Y. Shi, Reversal of histone methylation: Biochemical and molecular mechanisms of histone demethylases. Annu. Rev. Biochem. 79, 155-179 (2010).
24. A. Barski, S. Cuddapah, K. Cui, T.-Y. Roh, D. E. Schones, Z. Wang, G. Wei, I. Chepelev, K. Zhao, High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837 (2007).
25. X. Shen, Y. Liu, Y.-J. Hsu, Y. Fujiwara, J. Kim, X. Mao, G.-C. Yuan, S. H. Orkin, EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol. Cell 32, 491-502 (2008).
26. K. Agger, P. A. C. Cloos, J. Christensen, D. Pasini, S. Rose, J. Rappsilber, I. Issaeva, E. Canaani, A. E. Salcini, K. Helin, UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449, 731-734 (2007).
27. A. Broniscer, J. N. Baker, S. J. Baker, S. N. Chi, J. R. Geyer, E. B. Morris, A. Gajjar, Prospective collection of tissue samples at autopsy in children with diffuse intrinsic pontine glioma. Cancer 116, 4632-4637 (2010).
28. G. Deb, A. K. Singh, S. Gupta, EZH2: Not EZHY (easy) to deal. Mol. Cancer Res. 12, 639-653 (2014).
29. T. Ezponda, J. D. Licht, Molecular pathways: Deregulation of histone H3 lysine 27 methylation in cancer-Different paths, same destination. Clin. Cancer Res. 20, 5001-5008 (2014).
30. J. A. Simon, C. A. Lange, Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat. Res. 647, 21-29 (2008).
31. C. G. Kleer, Q. Cao, S. Varambally, R. Shen, I. Ota, S. A. Tomlins, D. Ghosh, R. G. A. B. Sewalt, A. P. Otte, D. F. Hayes, M. S. Sabel, D. Livant, S. J. Weiss, M. A. Rubin, A. M. Chinnaiyan, EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 100, 11606-11611 (2003).
32. S. Varambally, S. M. Dhanasekaran, M. Zhou, T. R. Barrette, C. Kumar-Sinha, M. G. Sanda, D. Ghosh, K. J. Pienta, R. G. A. B. Sewalt, A. P. Otte, M. A. Rubin, A. M. Chinnaiyan, The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624-629 (2002).
33. J. Van der Meulen, F. Speleman, P. Van Vlierberghe, The H3K27me3 demethylase UTX in normal development and disease. Epigenetics 9, 658-668 (2014).
34. Y. Gui, G. Guo, Y. Huang, X. Hu, A. Tang, S. Gao, R. Wu, C. Chen, X. Li, L. Zhou, M. He, Z. Li, X. Sun, W. Jia, J. Chen, S. Yang, F. Zhou, X. Zhao, S. Wan, R. Ye, C. Liang, Z. Liu, P. Huang, C. Liu, H. Jiang, Y. Wang, H. Zheng, L. Sun, X. Liu, Z. Jiang, D. Feng, J. Chen, S. Wu, J. Zou, Z. Zhang, R. Yang, J. Zhao, C. Xu, W. Yin, Z. Guan, J. Ye, H. Zhang, J. Li, K. Kristiansen, M. L. Nickerson, D. Theodorescu, Y. Li, X. Zhang, S. Li, J. Wang, H. Yang, J. Wang, Z. Cai, Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat. Genet. 43, 875-878 (2011).
35. J. S. Ross, K. Wang, R. N. Al-Rohil, T. Nazeer, C. E. Sheehan, G. A. Otto, J. He, G. Palmer, R. Yelensky, D. Lipson, S. Ali, S. Balasubramanian, J. A. Curran, L. Garcia, K. Mahoney, S. R. Downing, M. Hawryluk, V. A. Miller, P. J. Stephens, Advanced urothelial carcinoma: Next-generation sequencing reveals diverse genomic alterations and targets of therapy. Mod. Pathol. 27, 271-280 (2014).
36. K. Agger, P. A. C. Cloos, L. Rudkjær, K. Williams, G. Andersen, J. Christensen, K. Helin, The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev. 23, 1171-1176 (2009).
37. P. W. Lewis, M. M. Müller, M. S. Koletsky, F. Cordero, S. Lin, L. A. Banaszynski, B. A. Garcia, T. W. Muir, O. J. Becher, C. D. Allis, Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340, 857-861 (2013).
38. L. Bjerke, A. Mackay, M. Nandhabalan, A. Burford, A. Jury, S. Popov, D. A. Bax, D. Carvalho, K. R. Taylor, M. Vinci, I. Bajrami, I. M. McGonnell, C. J. Lord, R. M. Reis, D. Hargrave, A. Ashworth, P. Workman, C. Jones, Histone H3.3. mutations drive pediatric glioblastoma through upregulation of MYCN. Cancer Discov. 3, 512-519 (2013).
39. K.-M. Chan, D. Fang, H. Gan, R. Hashizume, C. Yu, M. Schroeder, N. Gupta, S. Mueller, C. D. James, R. Jenkins, J. Sarkaria, Z. Zhang, The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev. 27, 985-990 (2013).
40. T. Waldmann, R. Schneider, Targeting histone modifications-Epigenetics in cancer. Curr. Opin. Cell Biol. 25, 184-189 (2013).
41. P. Buczkowicz, C. Hoeman, P. Rakopoulos, S. Pajovic, L. Letourneau, M. Dzamba, A. Morrison, P. Lewis, E. Bouffet, U. Bartels, J. Zuccaro, S. Agnihotri, S. Ryall, M. Barszczyk, Y. Chornenkyy, M. Bourgey, G. Bourque, A. Montpetit, F. Cordero, P. Castelo-Branco, J. Mangerel, U. Tabori, K. C. Ho, A. Huang, K. R. Taylor, A. Mackay, A. E. Bendel, J. Nazarian, J. R. Fangusaro, M. A. Karajannis, D. Zagzag, N. K. Foreman, A. Donson, J. V. Hegert, A. Smith, J. Chan, L. Lafay-Cousin, S. Dunn, J. Hukin, C. Dunham, K. Scheinemann, J. Michaud, S. Zelcer, D. Ramsay, J. Cain, C. Brennan, M. M. Souweidane, C. Jones, C. D. Allis, M. Brudno, O. Becher, C. Hawkins, Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat. Genet. 46, 451-456 (2014).
42. G. Wu, A. K. Diaz, B. S. Paugh, S. L. Rankin, B. Ju, Y. Li, X. Zhu, C. Qu, X. Chen, J. Zhang, J. Easton, M. Edmonson, X. Ma, C. Lu, P. Nagahawatte, E. Hedlund, M. Rusch, S. Pounds, T. Lin, A. Onar-Thomas, R. Huether, R. Kriwacki, M. Parker, P. Gupta, J. Becksfort, L. Wei, H. L. Mulder, K. Boggs, B. Vadodaria, D. Yergeau, J. C. Russell, K. Ochoa, R. S. Fulton, L. L. Fulton, C. Jones, F. A. Boop, A. Broniscer, C. Wetmore, A. Gajjar, L. Ding, E. R. Mardis, R. K. Wilson, M. R. Taylor, J. R. Downing, D. W. Ellison, J. Zhang, S. J. Baker; St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project, The genomic landscape of diffuse intrinsic pontine glioma and pediatric nonbrainstem high-grade glioma. Nat. Genet. 46, 444-450 (2014).
43. O. J. Becher, R. J. Wechsler-Reya, For pediatric glioma, leave no histone unturned. Science 346, 1458-1459 (2014).
44. N. Gerges, A. M. Fontebasso, S. Albrecht, D. Faury, N. Jabado, Pediatric high-grade astrocytomas: A distinct neuro-oncological paradigm. Genome Med. 5, 66 (2013).
45. K. Aihara, A. Mukasa, K. Gotoh, K. Saito, G. Nagae, S. Tsuji, K. Tatsuno, S. Yamamoto, S. Takayanagi, Y. Narita, S. Shibui, H. Aburatani, N. Saito, H3F3A K27M mutations in thalamic gliomas from young adult patients. Neuro Oncol. 16, 140-146 (2014).
46. S. Bender, Y. Tang, A. M. Lindroth, V. Hovestadt, D. T. W. Jones, M. Kool, M. Zapatka, P. A. Northcott, D. Sturm, W. Wang, B. Radlwimmer, J. W. Hrjfeldt, N. Truffaux, D. Castel, S. Schubert, M. Ryzhova, H. Şeker-Cin, J. Gronych, P. D. Johann, S. Stark, J. Meyer, T. Milde, M. Schuhmann, M. Ebinger, C.-M. Monoranu, A. Ponnuswami, S. Chen, C. Jones, O. Witt, V. P. Collins, A. von Deimling, N. Jabado, S. Puget, J. Grill, K. Helin, A. Korshunov, P. Lichter, M. Monje, C. Plass, Y.-J. Cho, S. M. Pfister, Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24, 660-672 (2013).
47. S. Venneti, M. T. Garimella, L. M. Sullivan, D. Martinez, J. T. Huse, A. Heguy, M. Santi, C. B. Thompson, A. R. Judkins, Evaluation of histone 3 lysine 27 trimethylation (H3K27me3) and enhancer of Zest 2 (EZH2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3A K27M mutant glioblastomas. Brain Pathol. 23, 558-564 (2013).
48. T. H. A. Ederveen, I. K. Mandemaker, C. Logie, The human histone H3 complement anno 2011. Biochim. Biophys. Acta 1809, 577-586 (2011).
49. K. Funato, T. Major, P. W. Lewis, C. D. Allis, V. Tabar, Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation. Science 346, 1529-1533 (2014).
50. D. A. Bax, A. Mackay, S. E. Little, D. Carvalho, M. Viana-Pereira, N. Tamber, A. E. Grigoriadis, A. Ashworth, R. M. Reis, D. W. Ellison, S. Al-Sarraj, D. Hargrave, C. Jones, A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. Clin. Cancer Res. 16, 3368-3377 (2010).
51. B. S. Paugh, C. Qu, C. Jones, Z. Liu, M. Adamowicz-Brice, J. Zhang, D. A. Bax, B. Coyle, J. Barrow, D. Hargrave, J. Lowe, A. Gajjar, W. Zhao, A. Broniscer, D. W. Ellison, R. G. Grundy, S. J. Baker, Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J. Clin. Oncol. 28, 3061-3068 (2010).
52. G. Barone, J. Anderson, A. D. J. Pearson, K. Petrie, L. Chesler, New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK. Clin. Cancer Res. 19, 5814-5821 (2013).
53. A. Puissant, S. M. Frumm, G. Alexe, C. F. Bassil, J. Qi, Y. H. Chanthery, E. A. Nekritz, R. Zeid, W. C. Gustafson, P. Greninger, M. J. Garnett, U. McDermott, C. H. Benes, A. L. Kung, W. A. Weiss, J. E. Bradner, K. Stegmaier, Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 3, 308-323 (2013).
54. E. Szenker, D. Ray-Gallet, G. Almouzni, The double face of the histone variant H3.3. Cell Res. 21, 421-434 (2011).
55. P. Pathak, P. Jha, S. Purkait, V. Sharma, V. Suri, M. C. Sharma, M. Faruq, A. Suri, C. Sarkar, Altered global histone-trimethylation code and H3F3A-ATRX mutation in pediatric GBM. J. Neurooncol 121, 489-497 (2015).
56. M. A. Dawson, T. Kouzarides, Cancer epigenetics: From mechanism to therapy. Cell 150, 12-27 (2012).
57. R. Hashizume, N. Andor, Y. Ihara, R. Lerner, H. Gan, X. Chen, D. Fang, X. Huang, M. W. Tom, V. Ngo, D. Solomon, S. Mueller, P. L. Paris, Z. Zhang, C. Petritsch, N. Gupta, T. A. Waldman, C. D. James, Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat. Med. 20, 1394-1396 (2014).
58. M. R. Hübner, D. L. Spector, Role of H3K27 demethylases Jmjd3 and UTX in transcriptional regulation. Cold Spring Harb. Symp. Quant. Biol. 75, 43-49 (2010).
59. S. M. Kooistra, K. Helin, Molecular mechanisms and potential functions of histone demethylases. Nat. Rev. Mol. Cell Biol. 13, 297-311 (2012).
60. P. A. C. Cloos, J. Christensen, K. Agger, K. Helin, Erasing the methyl mark: Histone demethylases at the center of cellular differentiation and disease. Genes Dev. 22, 1115-1140 (2008).
61. L. Kruidenier, C.-w. Chung, Z. Cheng, J. Liddle, K. Che, G. Joberty, M. Bantscheff, C. Bountra, A. Bridges, H. Diallo, D. Eberhard, S. Hutchinson, E. Jones, R. Katso, M. Leveridge, P. K. Mander, J. Mosley, C. Ramirez-Molina, P. Rowland, C. J. Schofield, R. J. Sheppard, J. E. Smith, C. Swales, R. Tanner, P. Thomas, A. Tumber, G. Drewes, U. Oppermann, D. J. Patel, K. Lee, D. M. Wilson, A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488, 404-408 (2012).
62. P. Ntziachristos, A. Tsirigos, G. G. Welstead, T. Trimarchi, S. Bakogianni, L. Xu, E. Loizou, L. Holmfeldt, A. Strikoudis, B. King, J. Mullenders, J. Becksfort, J. Nedjic, E. Paietta, M. S. Tallman, J. M. Rowe, G. Tonon, T. Satoh, L. Kruidenier, R. Prinjha, S. Akira, P. Van Vlierberghe, A. A. Ferrando, R. Jaenisch, C. G. Mullighan, I. Aifantis, Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature 514, 513-517 (2014).
63. X. Wang, A. M. Dubuc, V. Ramaswamy, S. Mack, D. M. A. Gendoo, M. Remke, X. Wu, L. Garzia, B. Luu, F. Cavalli, J. Peacock, B. López, P. Skowron, D. Zagzag, D. Lyden, C. Hoffman, Y.-J. Cho, C. Eberhart, T. MacDonald, X.-N. Li, T. Van Meter, P. A. Northcott, B. Haibe-Kains, C. Hawkins, J. T. Rutka, E. Bouffet, S. M. Pfister, A. Korshunov, M. D. Taylor, Medulloblastoma subgroups remain stable across primary and metastatic compartments. Acta Neuropathol. 129, 449-457 (2015).
64. A. M. Dubuc, M. Remke, A. Korshunov, P. A. Northcott, S. H. Zhan, M. Mendez-Lago, M. Kool, D. T. W. Jones, A. Unterberger, A. S. Morrissy, D. Shih, J. Peacock, V. Ramaswamy, A. Rolider, X. Wang, H. Witt, T. Hielscher, C. Hawkins, R. Vibhakar, S. Croul, J. T. Rutka, W. A. Weiss, S. J. M. Jones, C. G. Eberhart, M. A. Marra, S. M. Pfister, M. D. Taylor, Aberrant patterns of H3K4 and H3K27 histone lysine methylation occur across subgroups in medulloblastoma. Acta Neuropathol. 125, 373-384 (2013).
65. S. C. Mack, H. Witt, R. M. Piro, L. Gu, S. Zuyderduyn, A. M. Stütz, X. Wang, M. Gallo, L. Garzia, K. Zayne, X. Zhang, V. Ramaswamy, N. Jäger, D. T. W. Jones, M. Sill, T. J. Pugh, M. Ryzhova, K. M. Wani, D. J. H. Shih, R. Head, M. Remke, S. D. Bailey, T. Zichner, C. C. Faria, M. Barszczyk, S. Stark, H. Seker-Cin, S. Hutter, P. Johann, S. Bender, V. Hovestadt, T. Tzaridis, A. M. Dubuc, P. A. Northcott, J. Peacock, K. C. Bertrand, S. Agnihotri, F. M. G. Cavalli, I. Clarke, K. Nethery-Brokx, C. L. Creasy, S. K. Verma, J. Koster, X. Wu, Y. Yao, T. Milde, P. Sin-Chan, J. Zuccaro, L. Lau, S. Pereira, P. Castelo-Branco, M. Hirst, M. A. Marra, S. S. Roberts, D. Fults, L. Massimi, Y. J. Cho, T. Van Meter, W. Grajkowska, B. Lach, A. E. Kulozik, A. von Deimling, O. Witt, S. W. Scherer, X. Fan, K. M. Muraszko, M. Kool, S. L. Pomeroy, N. Gupta, J. Phillips, A. Huang, U. Tabori, C. Hawkins, D. Malkin, P. N. Kongkham, W. A. Weiss, N. Jabado, J. T. Rutka, E. Bouffet, J. O. Korbel, M. Lupien, K. D. Aldape, G. D. Bader, R. Eils, P. Lichter, P. B. Dirks, S. M. Pfister, A. Korshunov, M. D. Taylor, Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506, 445-450 (2014).
66. J. Okosun, C. Bödör, J. Wang, S. Araf, C.-Y. Yang, C. Pan, S. Boller, D. Cittaro, M. Bozek, S. Iqbal, J. Matthews, D. Wrench, J. Marzec, K. Tawana, N. Popov, C. O'Riain, D. O'Shea, E. Carlotti, A. Davies, C. H. Lawrie, A. Matolcsy, M. Calaminici, A. Norton, R. J. Byers, C. Mein, E. Stupka, T. A. Lister, G. Lenz, S. Montoto, J. G. Gribben, Y. Fan, R. Grosschedl, C. Chelala, J. Fitzgibbon, Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat. Genet. 46, 176-181 (2014).
67. H.-M. Herz, M. Morgan, X. Gao, J. Jackson, R. Rickels, S. K. Swanson, L. Florens, M. P. Washburn, J. C. Eissenberg, A. Shilatifard, Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling. Science 345, 1065-1070 (2014).
68. G. J. Kitange, A. C. Mladek, B. L. Carlson, M. A. Schroeder, J. L. Pokorny, L. Cen, P. A. Decker, W. Wu, G. A. Lomberk, S. K. Gupta, R. A. Urrutia, J. N. Sarkaria, Inhibition of histone deacetylation potentiates the evolution of acquired temozolomide resistance linked to MGMT upregulation in glioblastoma xenografts. Clin. Cancer Res. 18, 4070-4079 (2012).
69. M. M. Singh, B. Johnson, A. Venkatarayan, E. R. Flores, J. Zhang, X. Su, M. Barton, F. Lang, J. Chandra, Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma. Neuro. Oncol. 17, 1463-1473 (2015).
70. T. Milde, S. Kleber, A. Korshunov, H. Witt, T. Hielscher, P. Koch, H.-G. Kopp, M. Jugold, H. E. Deubzer, I. Oehme, M. Lodrini, H.-J. Gröne, A. Benner, O. Brüstle, R. J. Gilbertson, A. von Deimling, A. E. Kulozik, S. M. Pfister, A. Martin-Villalba, O. Witt, A novel human high-risk ependymoma stem cell model reveals the differentiation-inducing potential of the histone deacetylase inhibitor Vorinostat. Acta Neuropathol. 122, 637-650 (2011).
71. C. S. Grasso, Y. Tang, N. Truffaux, N. E. Berlow, L. Liu, M.-A. Debily, M. J. Quist, L. E. Davis, E. C. Huang, P. J. Woo, A. Ponnuswami, S. Chen, T. B. Johung, W. Sun, M. Kogiso, Y. Du, L. Qi, Y. Huang, M. Hütt-Cabezas, K. E Warren, L. Le Dret, P. S. Meltzer, H. Mao, M. Quezado, D. G. van Vuurden, J. Abraham, M. Fouladi, M. N. Svalina, N. Wang, C. Hawkins, J. Nazarian, M. M. Alonso, E. H. Raabe, E. Hulleman, P. T Spellman, X.-N. Li, C. Keller, R. Pal, J. Grill, M. Monje, Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat. Med. 21, 555-559 (2015).
72. Z. Z. Brown, M. M. Müller, S. U. Jain, C. D. Allis, P. W. Lewis, T. W. Muir, Strategy for "detoxification" of a cancer-derived histone mutant based on mapping its interaction with the methyltransferase PRC2. J. Am. Chem. Soc. 136, 13498-13501 (2014).