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Histone Lysine-to-Methionine Mutation as Anticancer Drug Target

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Histone Mutations and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1283))

Abstract

Histone modification stands for a vital genetic information form, which shows tight correlation with the modulation of normal physiological activities by genes. Abnormal regulation of histone methylation due to histone modification enzyme changes and histone mutations plays an important role in the development of cancer. Histone mutations, especially H3K27M and H3K36M, have been identified in various cancers such as pediatric DIPG (diffuse intrinsic pontine glioma) and chondroblastoma respectively. “K to M” mutation results overall downregulation of methylation on these lysine residues. Also, “K to M” mutant histones can inhibit the enzymatic activity of the responsible HMT (histone methyltransferase); for instance, SETD2 indicates H3K36 methylation, and Ezh2 represents H3K27 methylation. In-depth analysis of the mechanism of tumor formation triggered by the K to M mutation results in possible targeted therapies. This chapter is going to briefly introduce the mechanism of histone lysine-to-methionine mutation and review the recently identified targeted therapeutic strategies.

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Abbreviations

DIPG:

Diffuse intrinsic pontine glioma

EZH2:

Enhancer of zeste homolog 2

H2A:

Histone H2A

H2B:

Histone H2B

KDM1A:

Lysine (K)-specific demethylase 1A

KDM1B:

Lysine (K)-specific demethylase 1B

References

  1. Woo YH, Li WH (2012) Evolutionary conservation of histone modifications in mammals. Mol Biol Evol 29(7):1757–1767

    Article  CAS  Google Scholar 

  2. Henneman B, van Emmerik C, van Ingen H, Dame RT (2018) Structure and function of archaeal histones. PLoS Genet 14(9):e1007582

    Article  Google Scholar 

  3. Kornberg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184(4139):868–871

    Article  CAS  Google Scholar 

  4. El Kennani S, Adrait A, Shaytan AK, Khochbin S, Bruley C, Panchenko AR, Landsman D, Pflieger D, Govin J (2017) MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones. Epigenetics Chromatin 10:2

    Article  Google Scholar 

  5. Ramachandran S, Henikoff S (2015) Replicating nucleosomes. Sci Adv 1(7):e1500587

    Article  Google Scholar 

  6. Bowman GD, Poirier MG (2015) Post-translational modifications of histones that influence nucleosome dynamics. Chem Rev 115(6):2274–2295

    Article  CAS  Google Scholar 

  7. Robinson KM, Schultz MC (2003) Replication-independent assembly of nucleosome arrays in a novel yeast chromatin reconstitution system involves antisilencing factor Asf1p and chromodomain protein Chd1p. Mol Cell Biol 23(22):7937–7946

    Article  CAS  Google Scholar 

  8. Mohammad F, Helin K (2017) Oncohistones: drivers of pediatric cancers. Genes Dev 31(23-24):2313–2324

    Article  CAS  Google Scholar 

  9. Kallappagoudar S, Yadav RK, Lowe BR, Partridge JF (2015) Histone H3 mutations--a special role for H3.3 in tumorigenesis? Chromosoma 124(2):177–189

    Article  CAS  Google Scholar 

  10. Liu X, McEachron TA, Schwartzentruber J, Wu G (2014) Histone H3 mutations in pediatric brain tumors. Cold Spring Harb Perspect Biol 6(4):a018689

    Article  Google Scholar 

  11. Lowe BR, Maxham LA, Hamey JJ, Wilkins MR, Partridge JF (2019) Histone H3 mutations: an updated view of their role in chromatin deregulation and cancer. Cancers 11(5)

    Google Scholar 

  12. Yang XJ, Seto E (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31(4):449–461

    Article  CAS  Google Scholar 

  13. Kanwal R, Gupta S (2012) Epigenetic modifications in cancer. Clin Genet 81(4):303–311

    Article  CAS  Google Scholar 

  14. Taby R, Issa JP (2010) Cancer epigenetics. CA Cancer J Clin 60(6):376–392

    Article  Google Scholar 

  15. Cheng X (1995) Structure and function of DNA methyltransferases. Annu Rev Biophys Biomol Struct 24:293–318

    Article  CAS  Google Scholar 

  16. Foda BM, Singh U (2015) Dimethylated H3K27 is a repressive epigenetic histone mark in the Protist Entamoeba histolytica and is significantly enriched in genes silenced via the RNAi pathway. J Biol Chem 290(34):21114–21130

    Article  CAS  Google Scholar 

  17. Hyun K, Jeon J, Park K, Kim J (2017) Writing, erasing and reading histone lysine methylations. Exp Mol Med 49(4):e324

    Article  CAS  Google Scholar 

  18. Hou H, Yu H (2010) Structural insights into histone lysine demethylation. Curr Opin Struct Biol 20(6):739–748

    Article  CAS  Google Scholar 

  19. Cloos PA, Christensen J, Agger K, Helin K (2008) Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 22(9):1115–1140

    Article  CAS  Google Scholar 

  20. Rothbart SB, Strahl BD (2014) Interpreting the language of histone and DNA modifications. Biochim Biophys Acta 1839(8):627–643

    Article  CAS  Google Scholar 

  21. Bottomley MJ (2004) Structures of protein domains that create or recognize histone modifications. EMBO Rep 5(5):464–469

    Article  CAS  Google Scholar 

  22. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395

    Article  CAS  Google Scholar 

  23. Zoghbi HY, Beaudet AL (2016) Epigenetics and human disease. Cold Spring Harb Perspect Biol 8(2):a019497

    Article  Google Scholar 

  24. Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E, Bartels U, Albrecht S, Schwartzentruber J, Letourneau L, Bourgey M, Bourque G, Montpetit A, Bourret G, Lepage P, Fleming A et al (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124(3):439–447

    Article  CAS  Google Scholar 

  25. 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 et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253

    Article  CAS  Google Scholar 

  26. Sturm D, Bender S, Jones DT, Lichter P, Grill J, Becher O, Hawkins C, Majewski J, Jones C, Costello JF, Iavarone A, Aldape K, Brennan CW, Jabado N, Pfister SM (2014) Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer 14(2):92–107

    Article  CAS  Google Scholar 

  27. Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M et al (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46(5):451–456

    Article  CAS  Google Scholar 

  28. Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N, Pages M, Taylor KR, Saulnier P, Lacroix L, Mackay A, Jones C, Sainte-Rose C, Blauwblomme T, Andreiuolo F, Puget S et al (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130(6):815–827

    Article  CAS  Google Scholar 

  29. Papillon-Cavanagh S, Lu C, Gayden T, Mikael LG, Bechet D, Karamboulas C, Ailles L, Karamchandani J, Marchione DM, Garcia BA, Weinreb I, Goldstein D, Lewis PW, Dancu OM, Dhaliwal S, Stecho W et al (2017) Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas. Nat Genet 49(2):180–185

    Article  CAS  Google Scholar 

  30. Shah MA, Denton EL, Arrowsmith CH, Lupien M, Schapira M (2014) A global assessment of cancer genomic alterations in epigenetic mechanisms. Epigenetics Chromatin 7(1):29

    Article  Google Scholar 

  31. Aihara K, Mukasa A, Gotoh K, Saito K, Nagae G, Tsuji S, Tatsuno K, Yamamoto S, Takayanagi S, Narita Y, Shibui S, Aburatani H, Saito N (2014) H3F3A K27M mutations in thalamic gliomas from young adult patients. Neuro-Oncology 16(1):140–146

    Article  CAS  Google Scholar 

  32. 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 et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482(7384):226–231

    Article  CAS  Google Scholar 

  33. Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P, Wedge DC, Cooke SL, Gundem G, Davies H, Nik-Zainal S, Martin S, McLaren S, Goodie V, Robinson B, Butler A et al (2013) Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet 45(12):1479–1482

    Article  CAS  Google Scholar 

  34. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tonjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22(4):425–437

    Article  CAS  Google Scholar 

  35. Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, Nikbakht H, Gerges N, Fiset PO, Bechet D, Faury D, De Jay N, Ramkissoon LA, Corcoran A, Jones DT, Sturm D, Johann P, Tomita T, Goldman S et al (2014) Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet 46(5):462–466

    Article  CAS  Google Scholar 

  36. Du TT, Huang QH (2007) The roles of histone lysine methylation in epigenetic regulation. Hereditas 29(4):387–392

    CAS  Google Scholar 

  37. Kimura H (2013) Histone modifications for human epigenome analysis. J Hum Genet 58(7):439–445

    Article  CAS  Google Scholar 

  38. Grossniklaus U, Paro R (2014) Transcriptional silencing by polycomb-group proteins. Cold Spring Harb Perspect Biol 6(11):a019331

    Article  Google Scholar 

  39. Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life. Nature 469(7330):343–349

    Article  CAS  Google Scholar 

  40. Yoo KH, Hennighausen L (2012) EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci 8(1):59–65

    Article  CAS  Google Scholar 

  41. Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V, Zlobin A, Diaz MO, Scacheri PC, Harte PJ (2009) CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136(18):3131–3141

    Article  CAS  Google Scholar 

  42. Paugh BS, Zhu X, Qu C, Endersby R, Diaz AK, Zhang J, Bax DA, Carvalho D, Reis RM, Onar-Thomas A, Broniscer A, Wetmore C, Zhang J, Jones C, Ellison DW, Baker SJ (2013) Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res 73(20):6219–6229

    Article  CAS  Google Scholar 

  43. Puget S, Philippe C, Bax DA, Job B, Varlet P, Junier MP, Andreiuolo F, Carvalho D, Reis R, Guerrini-Rousseau L, Roujeau T, Dessen P, Richon C, Lazar V, Le Teuff G, Sainte-Rose C et al (2012) Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PLoS One 7(2):e30313

    Article  CAS  Google Scholar 

  44. Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E et al (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46(5):444–450

    Article  CAS  Google Scholar 

  45. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820

    Article  Google Scholar 

  46. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M et al (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38(5):525–527

    Article  CAS  Google Scholar 

  47. Taylor KR, Mackay A, Truffaux N, Butterfield Y, Morozova O, Philippe C, Castel D, Grasso CS, Vinci M, Carvalho D, Carcaboso AM, de Torres C, Cruz O, Mora J, Entz-Werle N, Ingram WJ et al (2014) Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 46(5):457–461

    Article  CAS  Google Scholar 

  48. Yuen BT, Knoepfler PS (2013) Histone H3.3 mutations: a variant path to cancer. Cancer Cell 24(5):567–574

    Article  CAS  Google Scholar 

  49. Lewis PW, Muller MM, Koletsky MS, Cordero F, Lin S, Banaszynski LA, Garcia BA, Muir TW, Becher OJ, Allis CD (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340(6134):857–861

    Article  CAS  Google Scholar 

  50. Chan KM, Han J, Fang D, Gan H, Zhang Z (2013) A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo? Cell Cycle 12(16):2546–2552

    Article  CAS  Google Scholar 

  51. Justin N, Zhang Y, Tarricone C, Martin SR, Chen S, Underwood E, De Marco V, Haire LF, Walker PA, Reinberg D, Wilson JR, Gamblin SJ (2016) Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat Commun 7:11316

    Article  CAS  Google Scholar 

  52. Piunti A, Hashizume R, Morgan MA, Bartom ET, Horbinski CM, Marshall SA, Rendleman EJ, Ma Q, Takahashi YH, Woodfin AR, Misharin AV, Abshiru NA, Lulla RR, Saratsis AM, Kelleher NL, James CD et al (2017) Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas. Nat Med 23(4):493–500

    Article  CAS  Google Scholar 

  53. Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27(9):985–990

    Article  CAS  Google Scholar 

  54. Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M, Zapatka M, Northcott PA, Sturm D, Wang W, Radlwimmer B, Hojfeldt JW, Truffaux N, Castel D, Schubert S, Ryzhova M et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24(5):660–672

    Article  CAS  Google Scholar 

  55. Zarghooni M, Bartels U, Lee E, Buczkowicz P, Morrison A, Huang A, Bouffet E, Hawkins C (2010) Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28(8):1337–1344

    Article  CAS  Google Scholar 

  56. Larson JD, Kasper LH, Paugh BS, Jin H, Wu G, Kwon CH, Fan Y, Shaw TI, Silveira AB, Qu C, Xu R, Zhu X, Zhang J, Russell HR, Peters JL, Finkelstein D et al (2019) Histone H3.3 K27M accelerates spontaneous brainstem glioma and drives restricted changes in bivalent gene expression. Cancer Cell 35(1):140–155. e147

    Article  CAS  Google Scholar 

  57. Mohammad F, Weissmann S, Leblanc B, Pandey DP, Hojfeldt JW, Comet I, Zheng C, Johansen JV, Rapin N, Porse BT, Tvardovskiy A, Jensen ON, Olaciregui NG, Lavarino C, Sunol M, de Torres C et al (2017) EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nat Med 23(4):483–492

    Article  CAS  Google Scholar 

  58. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J et al (2013) The somatic genomic landscape of glioblastoma. Cell 155(2):462–477

    Article  CAS  Google Scholar 

  59. Fang D, Gan H, Lee JH, Han J, Wang Z, Riester SM, Jin L, Chen J, Zhou H, Wang J, Zhang H, Yang N, Bradley EW, Ho TH, Rubin BP, Bridge JA et al (2016) The histone H3.3K36M mutation reprograms the epigenome of chondroblastomas. Science 352(6291):1344–1348

    Article  CAS  Google Scholar 

  60. Lu C, Jain SU, Hoelper D, Bechet D, Molden RC, Ran L, Murphy D, Venneti S, Hameed M, Pawel BR, Wunder JS, Dickson BC, Lundgren SM, Jani KS, De Jay N, Papillon-Cavanagh S et al (2016) Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape. Science 352(6287):844–849

    Article  CAS  Google Scholar 

  61. Zhang Y, Shan CM, Wang J, Bao K, Tong L, Jia S (2017) Molecular basis for the role of oncogenic histone mutations in modulating H3K36 methylation. Sci Rep 7:43906

    Article  Google Scholar 

  62. Yang S, Zheng X, Lu C, Li GM, Allis CD, Li H (2016) Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase. Genes Dev 30(14):1611–1616

    Article  CAS  Google Scholar 

  63. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B (2011) H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem 286(10):7983–7989

    Article  CAS  Google Scholar 

  64. Schmitges FW, Prusty AB, Faty M, Stutzer A, Lingaraju GM, Aiwazian J, Sack R, Hess D, Li L, Zhou S, Bunker RD, Wirth U, Bouwmeester T, Bauer A, Ly-Hartig N, Zhao K et al (2011) Histone methylation by PRC2 is inhibited by active chromatin marks. Mol Cell 42(3):330–341

    Article  CAS  Google Scholar 

  65. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK et al (2012) A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488(7411):404–408

    Article  CAS  Google Scholar 

  66. Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V, Solomon D, Mueller S, Paris PL, Zhang Z, Petritsch C, Gupta N et al (2014) Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med 20(12):1394–1396

    Article  CAS  Google Scholar 

  67. Heinemann B, Nielsen JM, Hudlebusch HR, Lees MJ, Larsen DV, Boesen T, Labelle M, Gerlach LO, Birk P, Helin K (2014) Inhibition of demethylases by GSK-J1/J4. Nature 514(7520):E1–E2

    Article  CAS  Google Scholar 

  68. Grasso CS, Tang Y, Truffaux N, Berlow NE, Liu L, Debily MA, Quist MJ, Davis LE, Huang EC, Woo PJ, Ponnuswami A, Chen S, Johung TB, Sun W, Kogiso M, Du Y et al (2015) Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med 21(7):827

    Article  CAS  Google Scholar 

  69. Hennika T, Hu G, Olaciregui NG, Barton KL, Ehteda A, Chitranjan A, Chang C, Gifford AJ, Tsoli M, Ziegler DS, Carcaboso AM, Becher OJ (2017) Pre-clinical study of Panobinostat in xenograft and genetically engineered murine diffuse intrinsic pontine glioma models. PLoS One 12(1):e0169485

    Article  Google Scholar 

  70. Funato K, Major T, Lewis PW, Allis CD, Tabar V (2014) Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation. Science 346(6216):1529–1533

    Article  CAS  Google Scholar 

  71. Borkin D, He S, Miao H, Kempinska K, Pollock J, Chase J, Purohit T, Malik B, Zhao T, Wang J, Wen B, Zong H, Jones M, Danet-Desnoyers G, Guzman ML, Talpaz M et al (2015) Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 27(4):589–602

    Article  CAS  Google Scholar 

  72. Pfister SX, Markkanen E, Jiang Y, Sarkar S, Woodcock M, Orlando G, Mavrommati I, Pai CC, Zalmas LP, Drobnitzky N, Dianov GL, Verrill C, Macaulay VM, Ying S, La Thangue NB, D'Angiolella V et al (2015) Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation. Cancer Cell 28(5):557–568

    Article  CAS  Google Scholar 

  73. Fu S, Wang Y, Keyomarsi K, Meric-Bernstam F, Meric-Bernstein F (2018) Strategic development of AZD1775, a Wee1 kinase inhibitor, for cancer therapy. Expert Opin Investig Drugs 27(9):741–751

    Article  CAS  Google Scholar 

  74. Chase A, Cross NC (2011) Aberrations of EZH2 in cancer. Clin Cancer Res 17(9):2613–2618

    Article  CAS  Google Scholar 

  75. Kanu N, Gronroos E, Martinez P, Burrell RA, Yi Goh X, Bartkova J, Maya-Mendoza A, Mistrik M, Rowan AJ, Patel H, Rabinowitz A, East P, Wilson G, Santos CR, McGranahan N, Gulati S et al (2015) SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair. Oncogene 34(46):5699–5708

    Article  CAS  Google Scholar 

  76. Kim IK, McCutcheon JN, Rao G, Liu SV, Pommier Y, Skrzypski M, Zhang YW, Giaccone G (2019) Acquired SETD2 mutation and impaired CREB1 activation confer cisplatin resistance in metastatic non-small cell lung cancer. Oncogene 38(2):180–193

    Article  CAS  Google Scholar 

  77. Dunn J, Rao S (2017) Epigenetics and immunotherapy: the current state of play. Mol Immunol 87:227–239

    Article  CAS  Google Scholar 

  78. Mazzone R, Zwergel C, Mai A, Valente S (2017) Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy. Clin Epigenetics 9:59

    Article  Google Scholar 

  79. Kelly AD, Issa JJ (2017) The promise of epigenetic therapy: reprogramming the cancer epigenome. Curr Opin Genet Dev 42:68–77

    Article  CAS  Google Scholar 

  80. Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, Han J, Wei X (2019) Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther 4:62

    Article  Google Scholar 

  81. Dawson MA (2017) The cancer epigenome: concepts, challenges, and therapeutic opportunities. Science 355(6330):1147–1152

    Article  CAS  Google Scholar 

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  1. Jianhong Yang and Qiang Qiu contributed equally with all other contributors.

Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy and Cancer, Chengdu, China

    Jianhong Yang, Qiang Qiu & Lijuan Chen

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  1. Jianhong Yang
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  1. Institute of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China

    Dong Fang

  2. State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China

    Junhong Han

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Yang, J., Qiu, Q., Chen, L. (2021). Histone Lysine-to-Methionine Mutation as Anticancer Drug Target. In: Fang, D., Han, J. (eds) Histone Mutations and Cancer. Advances in Experimental Medicine and Biology, vol 1283. Springer, Singapore. https://doi.org/10.1007/978-981-15-8104-5_7

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