The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.
The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.
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DOI：
10.1038/ng.2938
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发表时间：
2014-05
期刊：
影响因子：
30.8
通讯作者：
Baker SJ
中科院分区：
文献类型：
--
作者：
Wu G;Diaz AK;Paugh BS;Rankin SL;Ju B;Li Y;Zhu X;Qu C;Chen X;Zhang J;Easton J;Edmonson M;Ma X;Lu C;Nagahawatte P;Hedlund E;Rusch M;Pounds S;Lin T;Onar-Thomas A;Huether R;Kriwacki R;Parker M;Gupta P;Becksfort J;Wei L;Mulder HL;Boggs K;Vadodaria B;Yergeau D;Russell JC;Ochoa K;Fulton RS;Fulton LL;Jones C;Boop FA;Broniscer A;Wetmore C;Gajjar A;Ding L;Mardis ER;Wilson RK;Taylor MR;Downing JR;Ellison DW;Zhang J;Baker SJ
儿童高级别胶质瘤(HGG)是一种破坏性疾病，两年存活率不到20%。我们通过全基因组、全外显子组和/或转录组测序分析了127例儿童HGG，包括弥漫性桥脑胶质瘤(DIPGs)和非脑干HGGs(NBS-HGGs)。除了先前报道的组蛋白H3、TP53和ATRX在DIPG和NBS-HGG中频繁的体细胞突变外，我们还发现ACVR1中反复出现的体细胞突变仅见于DIPG(32%)。在47%的DIPG和NBS-HGG中发现了产生融合基因的结构变异，40%的NBS-HGG中有40%的NBS-HGG反复融合涉及神经营养素受体基因NTRK1、2或3。针对受体酪氨酸激酶/RAS/PI3K信号转导、组蛋白修饰或染色质重塑和细胞周期调控的突变分别发生在68%、73%和59%的儿童HGG中，包括DIPGs和NBS-HGGs。这一全面的分析提供了对脑干内外驱动儿科HGG的独特和共享途径的洞察。
Pediatric high-grade glioma (HGG) is a devastating disease with a two-year survival of less than 20%. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs) by whole genome, whole exome, and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPG (32%), in addition to the previously reported frequent somatic mutations in histone H3, TP53 and ATRX in both DIPG and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, 2, or 3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase/RAS/PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59%, respectively, of pediatric HGGs, including DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.
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影响因子：
20.3
作者：
Eguchi, M;Eguchi-Ishimae, M;Kamada, N
通讯作者：
Kamada, N
影响因子：
3
作者：
Harel, Liraz;Costa, Barbara;Fainzilber, Mike
通讯作者：
Fainzilber, Mike
影响因子：
3.9
作者：
Li, Gordon;Mitra, Siddhartha S.;Wong, Albert J.
通讯作者：
Wong, Albert J.
DOI：
10.1083/jcb.201210031
发表时间：
2013-05-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kleiblova P;Shaltiel IA;Benada J;Ševčík J;Pecháčková S;Pohlreich P;Voest EE;Dundr P;Bartek J;Kleibl Z;Medema RH;Macurek L
通讯作者：
Macurek L
DOI：
10.1074/jbc.m112.365932
发表时间：
2012-10-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chaikuad A;Alfano I;Kerr G;Sanvitale CE;Boergermann JH;Triffitt JT;von Delft F;Knapp S;Knaus P;Bullock AN
通讯作者：
Bullock AN