Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lee, W; Teckie, S; Wiesner, T; Ran, L; Prieto Granada, CN; Lin, M; Zhu, S; Cao, Z; Liang, Y; Sboner, A; Tap, WD; Fletcher, JA; Huberman, KH; Qin, LX; Viale, A; Singer, S; Zheng, D; Berger, MF; Chen, Y; Antonescu, CR; Chi, P.
PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors.
Nat Genet. 2014; 46(11): 1227-1232.
Doi: 10.1038/ng.3095
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- Führende Autor*innen der Med Uni Graz
- Wiesner Thomas
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Base Sequence -
- Cell Line, Tumor -
- Chromatin Immunoprecipitation -
- Cyclin-Dependent Kinase Inhibitor p16 - genetics
- DNA Methylation -
- DNA Primers - genetics
- Gene Expression Profiling -
- Gene Expression Regulation, Neoplastic - genetics
- Genomics - methods
- Histones - metabolism
- Humans -
- Immunohistochemistry -
- Molecular Sequence Data -
- Mutation - genetics
- Neurilemmoma - genetics
- Neurofibromin 1 - genetics
- Polycomb Repressive Complex 2 - genetics Polycomb Repressive Complex 2 - metabolism
- Real-Time Polymerase Chain Reaction -
- Sequence Analysis, DNA -