Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis.
Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis.
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DOI：
10.1038/ng.2641
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发表时间：
2013-07
期刊：
影响因子：
30.8
通讯作者：
Largaespada, David A.
中科院分区：
文献类型：
--
作者：
Rahrmann, Eric P.;Watson, Adrienne L.;Keng, Vincent W.;Choi, Kwangmin;Moriarity, Branden S.;Beckmann, Dominic A.;Wolf, Natalie K.;Sarver, Aaron;Collins, Margaret H.;Moertel, Christopher L.;Wallace, Margaret R.;Gel, Bernat;Serra, Eduard;Ratner, Nancy;Largaespada, David A.
Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas of Schwann cell-lineage origin that occur sporadically or in association with the inherited syndrome, Neurofibromatosis Type 1. To identify genetic drivers of MPNST development, we utilized the Sleeping Beauty (SB) transposon-based somatic mutagenesis system in mice with somatic loss of tumor protein p53 (Trp53) function and/or overexpression of epidermal growth factor receptor (EGFR). Common insertion site (CIS) analysis of 269 neurofibromas and 106 MPNSTs identified 695 and 87 sites with a statistically significant number of recurrent transposon insertions, respectively. Comparison to human data sets revealed novel and known driver genes for MPNST formation at these sites. Pairwise co-occurrence analysis of CIS-associated genes identified many cooperating mutations that are enriched for in Wnt/CTNNB1, PI3K/Akt/mTor, and growth factor receptor signaling pathways. Lastly, we identified several novel proto-oncogenes including forkhead box R2 (Foxr2), which we functionally validated as a proto-oncogene involved in MPNST maintenance.
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影响因子：
5.7
作者：
Ghadimi MP;Lopez G;Torres KE;Belousov R;Young ED;Liu J;Brewer KJ;Hoffman A;Lusby K;Lazar AJ;Pollock RE;Lev D
通讯作者：
Lev D
影响因子：
7
作者：
Feber, Andrew;Wilson, Gareth A.;Beck, Stephan
通讯作者：
Beck, Stephan
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
45.3
作者：
Carli, M;Ferrari, A;Treuner, J
通讯作者：
Treuner, J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y