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Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status"

Nature Medicine volume 22, pages 578–579 (2016)Cite this article

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LaFave et al. reply

We recently reported that Bap1-null hematopoietic cells and BAP1-mutant mesothelioma cells were dependent on EZH2 for transformation, using both genetic and pharmacologic approaches to demonstrate EZH2 dependency in vivo1. We therefore read with great interest the work by Schoumacher et al.2, which investigated the role of EZH2 in BAP1-mutant uveal melanoma. In this study, the authors did not note any relationship between BAP1 mutations and EZH2 catalytic function, as assessed through studies with a small molecule inhibitor of EZH2. As has become clear in recent studies, epigenetic regulation and dependency on specific epigenetic regulatory complexes is often context dependent3,4. Given the central role of epigenetic regulation in differentiation and in tissue-specific gene regulation, it is therefore not unexpected that there may be differences in the relationship between BAP1 and EZH2 function in different tissue types and in different malignancies. We would, however, like to note several important points relating to EZH2 dependency in BAP1-mutant malignancies—and more generally to assessing dependencies on epigenetic regulatory complexes in different tumor types—as these issues are germane to the data presented by Schoumacher et al.2.

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Authors and Affiliations

  1. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Lindsay M LaFave, Barbara Spitzer, Efthymia Papalexi, Matthew D Keller, Todd Hricik, Katerina Konstantinoff, Jean-Baptiste Micol, Benjamin Durham, Young Rock Chung, Omar Abdel-Wahab & Ross L Levine

  2. Gerstner Sloan Kettering School of Biomedical Sciences, New York, New York, USA

    Lindsay M LaFave

  3. Department of Hematology–Oncology, Weill Cornell Medical College, New York, New York, USA

    Wendy Béguelin, Matt Teater & Ari Melnick

  4. The Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Richard Koche, Alan Chramiec, Andrei V Krivtsov, Scott A Armstrong & Ross L Levine

  5. Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Richard Koche & Scott A Armstrong

  6. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Barbara Spitzer & Scott A Armstrong

  7. Epizyme, Inc., Cambridge, Massachusetts, USA

    Sarah K Knutson, John E Campbell & Heike Keilhack

  8. Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York

    Gil Blum & Minkui Luo

  9. Tri-Institutional Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Gil Blum

  10. Chemical Synthesis Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Xinxu Shi & Ouathek Ouerfelli

  11. Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA

    Emma H Doud, Paul M Thomas & Neil L Kelleher

  12. Anti-Tumor Assessment Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Inna Khodos & Elisa de Stanchina

  13. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Prasad S Adusumilli

  14. Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Omar Abdel-Wahab & Ross L Levine

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  1. Lindsay M LaFave
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Correspondence to Ross L Levine.

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LaFave, L., Béguelin, W., Koche, R. et al. Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status". Nat Med 22, 578–579 (2016). https://doi.org/10.1038/nm.4094

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