The histone-modifying PRC2 complex has an ambiguous role in cancer, bearing both oncogenic and tumor-suppressive features depending on cell type. Studies of malignant peripheral nerve sheath tumors (MPNSTs) have now identified loss-of-function mutations altering PRC2 subunits, leading to the amplification of Ras-driven transcription and conferring vulnerability to BRD4 inhibitors.
References
Di Croce, L. & Helin, K. Nat. Struct. Mol. Biol. 20, 1147–1155 (2013).
Bracken, A.P. et al. EMBO J. 22, 5323–5335 (2003).
Ernst, T. et al. Nat. Genet. 42, 722–726 (2010).
Lee, W. et al. Nat. Genet. 46, 1227–1232 (2014).
Zhang, M. et al. Nat. Genet. 46, 1170–1172 (2014).
Basu, T.N. et al. Nature 356, 713–715 (1992).
De Raedt, T. et al. Nature doi:10.1038/nature13561 (13 August 2014).
Pasini, D. et al. Nucleic Acids Res. 38, 4958–4969 (2010).
Filippakopoulos, P. et al. Cell 149, 214–231 (2012).
Filippakopoulos, P. et al. Nature 468, 1067–1073 (2010).
Jessen, W.J. et al. J. Clin. Invest. 123, 340–347 (2013).
McCabe, M.T. & Creasy, C.L. Epigenomics 6, 341–351 (2014).
Downward, J. Nat. Rev. Cancer 3, 11–22 (2003).
Lewis, P.W. et al. Science 340, 857–861 (2013).
Iliopoulos, D. et al. Mol. Cell 39, 761–772 (2010).
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Baude, A., Lindroth, A. & Plass, C. PRC2 loss amplifies Ras signaling in cancer. Nat Genet 46, 1154–1155 (2014). https://doi.org/10.1038/ng.3124
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DOI: https://doi.org/10.1038/ng.3124
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