**8. Conclusions**

The advance of NGS enabled the discovery of PRC2 loss in MPNSTs, and the loss of H3K27me3 has become a clinically useful, sensitive, and specific marker for diagnosis. E fforts to understand the consequences of PRC2 loss in MPNST tumorigenesis and to identify novel vulnerabilities in this di fficult to treat tumor are areas of intensive focus for both basic and translational researchers. Recent works have discovered that the loss of PRC2 in MPNST likely a ffects changes in cellular signaling and immune surveillance through alteration of the core epigenetic and transcriptomic landscape in a neuronal specific precursor cell. Further studies will be enabled through a new generation of clinically annotated and genetically profiled patient samples and their derivative MPNST cell lines and PDX models, as well as GEMMs that mimic the clinically observed disease progression from benign plexiform neurofibroma through atypical neurofibroma to MPNST. These and other anticipated advances will hopefully accelerate discovery of mechanistically based strategies for the treatment of this devastating tumor.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2073-4425/11/3/287/s1, Table S1: Summary of mutations of *SUZ12* and *EED* in human MPNSTs.

**Author Contributions:** All authors researched relevant literature, conceived, wrote and edited the manuscript. All authors have read and agreed to the published version of the manuscript.

**Acknowledgments:** This work was funded by the Center for Cancer Research, Intramural Research Program at the National Cancer Institute. G.M. was supported by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, the Colgate-Palmolive Company, and other private donors. B.M. was supported by the National Cancer Institute-Queen's University Belfast Graduate Partnership Program, supported by contribution from the Northern Ireland Health and Social Care Research and Development Division. The authors thank Dr. Brigitte Widemann who provided insight and expertise that greatly improved this manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.
