Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations.
Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations.
复制标题
泛神经母细胞瘤分析揭示了年龄和签名相关的驱动程序改变。
DOI：
10.1038/s41467-020-18987-4
复制
发表时间：
2020-10-14
影响因子：
16.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Brady SW;Liu Y;Ma X;Gout AM;Hagiwara K;Zhou X;Wang J;Macias M;Chen X;Easton J;Mulder HL;Rusch M;Wang L;Nakitandwe J;Lei S;Davis EM;Naranjo A;Cheng C;Maris JM;Downing JR;Cheung NV;Hogarty MD;Dyer MA;Zhang J
神经母细胞瘤是一种儿科恶性肿瘤，临床结局不一。为了更好地了解神经母细胞瘤的发病机制，在这里，我们分析了702个神经母细胞瘤样本的全基因组，全外显子组和/或转录组数据。40%的样本至少有一个复发性驱动基因改变，大多数畸变，包括MYCN，ATRX和TERT改变，在不同年龄的频率不同。MYCN改变发生在中位年龄2.3岁，TERT发生在3.8岁，ATRX发生在5.6岁。COSMIC突变特征18，以前与活性氧相关，是神经母细胞瘤中驱动点突变的最常见原因，包括大多数ALK和Ras激活变体。信号18出现较早，并在整个疾病演变过程中持续存在。Signature 18在神经母细胞瘤中富集，具有MYCN扩增、17 q增加以及线粒体核糖体和电子传递相关基因表达增加。6例患者的复发性FGFR 1变异和5例样本中的ALK N-末端结构改变，确定了可能适合精确治疗的其他患者。神经母细胞瘤的基因组分析揭示了重要的疾病病因。在这项研究中，作者收集了来自700多个神经母细胞瘤的全基因组，外显子组和转录组数据，并确定了与年龄相关的分子特征，以及在较小的队列中被忽视的罕见的潜在靶向变异。
Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most ALK and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy. Genomic analysis of neuroblastoma has revealed important disease etiology. In this study, the authors assembled whole genome, exome and transcriptome data from over 700 neuroblastomas and identified molecular signatures correlated with age, and rare, potentially targetable variants overlooked in smaller cohorts.
登录
查看更多内容
影响因子：
3.7
作者：
George RE;Attiyeh EF;Li S;Moreau LA;Neuberg D;Li C;Fox EA;Meyerson M;Diller L;Fortina P;Look AT;Maris JM
通讯作者：
Maris JM
复发的神经母细胞瘤显示出频繁的RAS-MAPK途径突变。
影响因子：
30.8
作者：
Eleveld TF;Oldridge DA;Bernard V;Koster J;Colmet Daage L;Diskin SJ;Schild L;Bentahar NB;Bellini A;Chicard M;Lapouble E;Combaret V;Legoix-Né P;Michon J;Pugh TJ;Hart LS;Rader J;Attiyeh EF;Wei JS;Zhang S;Naranjo A;Gastier-Foster JM;Hogarty MD;Asgharzadeh S;Smith MA;Guidry Auvil JM;Watkins TB;Zwijnenburg DA;Ebus ME;van Sluis P;Hakkert A;van Wezel E;van der Schoot CE;Westerhout EM;Schulte JH;Tytgat GA;Dolman ME;Janoueix-Lerosey I;Gerhard DS;Caron HN;Delattre O;Khan J;Versteeg R;Schleiermacher G;Molenaar JJ;Maris JM
通讯作者：
Maris JM
影响因子：
8.8
作者：
Chen X;Bahrami A;Pappo A;Easton J;Dalton J;Hedlund E;Ellison D;Shurtleff S;Wu G;Wei L;Parker M;Rusch M;Nagahawatte P;Wu J;Mao S;Boggs K;Mulder H;Yergeau D;Lu C;Ding L;Edmonson M;Qu C;Wang J;Li Y;Navid F;Daw NC;Mardis ER;Wilson RK;Downing JR;Zhang J;Dyer MA;St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project
DOI：
10.1056/nejmoa1001527
发表时间：
2010-09-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baker DL;Schmidt ML;Cohn SL;Maris JM;London WB;Buxton A;Stram D;Castleberry RP;Shimada H;Sandler A;Shamberger RC;Look AT;Reynolds CP;Seeger RC;Matthay KK;Children’s Oncology Group
通讯作者：
Children’s Oncology Group
影响因子：
11.5
作者：
De Brouwer, Sara;De Preter, Katleen;Speleman, Frank
通讯作者：
Speleman, Frank