219
Views
0
CrossRef citations to date
0
Altmetric
Editorial

Epigenetic Reprogramming in Solid Tumors: Therapeutic Implications of EZH2 Gain-Of-Function Mutations

, &
Pages 687-690 | Published online: 28 Aug 2015

References

  • Kandoth C , McLellanMD , VandinFet al. Mutational landscape and significance across 12 major cancer types . Nature502 ( 7471 ), 333 – 339 ( 2013 ).
  • Helin K , DhanakD . Chromatin proteins and modifications as drug targets . Nature502 ( 7472 ), 480 – 488 ( 2013 ).
  • Suva ML , RiggiN , BernsteinBE . Epigenetic reprogramming in cancer . Science339 ( 6127 ), 1567 – 1570 ( 2013 ).
  • Bracken AP , HelinK . Polycomb group proteins: navigators of lineage pathways led astray in cancer . Nat. Rev. Cancer9 ( 11 ), 773 – 784 ( 2009 ).
  • Sparmann A , Van LohuizenM . Polycomb silencers control cell fate, development and cancer . Nat. Rev. Cancer6 ( 11 ), 846 – 856 ( 2006 ).
  • McCabe MT , CreasyCL . EZH2 as a potential target in cancer therapy . Epigenomics6 ( 3 ), 341 – 351 ( 2014 ).
  • Bachmann IM , HalvorsenOJ , CollettKet al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast . J. Clin. Oncol.24 ( 2 ), 268 – 273 ( 2006 ).
  • Morin RD , JohnsonNA , SeversonTMet al. Somatic mutations altering EZH2 (tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin . Nat. Genet.42 ( 2 ), 181 – 185 ( 2010 ).
  • Bodor C , GrossmannV , PopovNet al. EZH2 mutations are frequent and represent an early event in follicular lymphoma . Blood122 ( 18 ), 3165 – 3168 ( 2013 ).
  • Ott HM , GravesAP , PappalardiMBet al. A687V EZH2 is a driver of histone H3 lysine 27 (H3K27) hypertrimethylation . Mol. Cancer Ther.13 ( 12 ), 3062 – 3073 ( 2014 ).
  • Hodis E , WatsonIR , KryukovGVet al. A landscape of driver mutations in melanoma . Cell150 ( 2 ), 251 – 263 ( 2012 ).
  • Krauthammer M , KongY , HaBHet al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma . Nat. Genet.44 ( 9 ), 1006 – 1014 ( 2012 ).
  • Sneeringer CJ , ScottMP , KuntzKWet al. 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. USA107 ( 49 ), 20980 – 20985 ( 2010 ).
  • McCabe MT , OttHM , GanjiGet al. EZH2 inhibition as a therapeutic strategy for lymphoma with ezh2-activating mutations . Nature492 ( 7427 ), 108 – 112 ( 2012 ).
  • Knutson SK , KawanoS , MinoshimaYet al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-hodgkin lymphoma . Mol. Cancer Ther.13 ( 4 ), 842 – 854 ( 2014 ).
  • Beguelin W , PopovicR , TeaterMet al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation . Cancer Cell23 ( 5 ), 677 – 692 ( 2013 ).
  • Barsotti AM , RyskinM , ZhongWet al. Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth . Oncotarget6 ( 5 ), 2928 – 2938 ( 2015 ).
  • Zingg D , DebbacheJ , SchaeferSMet al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors . Nat. Commun.6 , 6051 ( 2015 ).
  • Shen C , VakocCR . Gain-of-function mutation of chromatin regulators as a tumorigenic mechanism and an opportunity for therapeutic intervention . Curr. Opin. Oncol.27 ( 1 ), 57 – 63 ( 2015 ).
  • Tiffen J , GallagherSJ , HerseyP . EZH2: An emerging role in melanomabiology and strategi es for targeted therapy . Pigment Cell Melanoma Res.28 ( 1 ), 21 – 30 ( 2015 ).
  • McHugh JB , FullenDR , MaL , KleerCG , SuLD . Expression of polycombgroup protein EZH2 in nevi and melanoma . J. Cutan. Pathol.34 ( 8 ), 597 – 600 ( 2007 ).
  • Ahuja N , EaswaranH , BaylinSB . Harnessing the potential of epigenetic therapy to targetsolid tumors . J. Clin. Invest.124 ( 1 ), 56 – 63 ( 2014 ).
  • Azad N , ZahnowCA , RudinCM , BaylinSB . The future of epigenetic therapyin solid tumours – lessons from the past . Nat. Rev. Clin. Oncol.10 ( 5 ), 256 – 266 ( 2013 ).
  • Dupage M , ChopraG , QuirosJet al. The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation . Immunity42 ( 2 ), 227 – 238 ( 2015 ).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.