PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors Journal Article


Authors: Lee, W.; Teckie, S.; Wiesner, T.; Ran, L.; Prieto Granada, C. N.; Lin, M.; Zhu, S.; Cao, Z.; Liang, Y.; Sboner, A.; Tap, W. D.; Fletcher, J. A.; Huberman, K. H.; Qin, L. X.; Viale, A.; Singer, S.; Zheng, D.; Berger, M. F.; Chen, Y.; Antonescu, C. R.; Chi, P.
Article Title: PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors
Abstract: Malignant peripheral nerve sheath tumors (MPNSTs) represent a group of highly aggressive soft-tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1 associated) or after radiotherapy. Using comprehensive genomic approaches, we identified loss-of-function somatic alterations of the Polycomb repressive complex 2 (PRC2) components (EED or SUZ12) in 92% of sporadic, 70% of NF1-associated and 90% of radiotherapy-associated MPNSTs. MPNSTs with PRC2 loss showed complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3) and aberrant transcriptional activation of multiple PRC2-repressed homeobox master regulators and their regulated developmental pathways. Introduction of the lost PRC2 component in a PRC2-deficient MPNST cell line restored H3K27me3 levels and decreased cell growth. Additionally, we identified frequent somatic alterations of CDKN2A (81% of all MPNSTs) and NF1 (72% of non-NF1-associated MPNSTs), both of which significantly co-occur with PRC2 alterations. The highly recurrent and specific inactivation of PRC2 components, NF1 and CDKN2A highlights their critical and potentially cooperative roles in MPNST pathogenesis.
Journal Title: Nature Genetics
Volume: 46
Issue: 11
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2014-11-01
Start Page: 1227
End Page: 1232
Language: English
DOI: 10.1038/ng.3095
PROVIDER: scopus
PMCID: PMC4249650
PUBMED: 25240281
DOI/URL:
Notes: Export Date: 1 December 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Yu Chen
    67 Chen
  2. Cristina R Antonescu
    609 Antonescu
  3. Ping Chi
    45 Chi
  4. Li-Xuan Qin
    115 Qin
  5. Sewit Teckie
    15 Teckie
  6. Samuel Singer
    229 Singer
  7. Agnes Viale
    205 Viale
  8. Thomas Wiesner
    38 Wiesner
  9. Michael Forman Berger
    386 Berger
  10. William Douglas Tap
    125 Tap
  11. Leili Ran
    17 Ran
  12. Zhen Cao
    15 Cao
  13. Yupu Liang
    8 Liang
  14. William Lee
    38 Lee
  15. Sinan Zhu
    2 Zhu