Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

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. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Wiesner Thomas
Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Number of Figures: 4
| | | |
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 -

© Med Uni Graz Impressum