Back to Search
Start Over
PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors.
- Source :
-
Nature Genetics . Nov2014, Vol. 46 Issue 11, p1227-1232. 6p. - Publication Year :
- 2014
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10614036
- Volume :
- 46
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Nature Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 99111177
- Full Text :
- https://doi.org/10.1038/ng.3095