The genomic landscape of pediatric myelodysplastic syndromes.
The genomic landscape of pediatric myelodysplastic syndromes.
复制标题
DOI：
10.1038/s41467-017-01590-5
复制
发表时间：
2017-11-16
影响因子：
16.6
通讯作者：
Klco JM
中科院分区：
文献类型：
--
作者：
Schwartz JR;Ma J;Lamprecht T;Walsh M;Wang S;Bryant V;Song G;Wu G;Easton J;Kesserwan C;Nichols KE;Mullighan CG;Ribeiro RC;Klco JM
骨髓增生异常综合征（MDS）在儿童中不常见，预后不良。与成人MDS相反，对儿科MDS的基因组景观知之甚少。在这里，我们使用全外显子组测序，靶向扩增子测序，和/或RNA测序的46例儿童原发性MDS患者的儿童MDS的体细胞和生殖细胞的变化。我们的数据显示，与成人MDS相比，Ras/MAPK通路突变在儿科MDS中常见（45%的主要队列），而RNA剪接基因突变罕见（2%的主要队列）。令人惊讶的是，SAMD 9或SAMD 9 L中的生殖系变体存在于17%的原发性MDS患者中，并且这些变体在肿瘤细胞中通常通过染色体缺失而丢失（例如，单体7）或拷贝数中性杂合性丢失（CN-LOH）。我们的数据证实成人和儿童MDS是具有不同机制的不同疾病，SAMD 9/SAMD 9 L突变代表了一类新的MDS易感性。骨髓增生异常综合征（MDS）在儿童中不常见，预后不良。在这里，作者询问了MDS的基因组景观，证实成人和儿童MDS是具有不同机制的独立疾病，并强调SAMD 9/SAMD 9 L突变代表了一类新的MDS易感性。
Myelodysplastic syndromes (MDS) are uncommon in children and have a poor prognosis. In contrast to adult MDS, little is known about the genomic landscape of pediatric MDS. Here, we describe the somatic and germline changes of pediatric MDS using whole exome sequencing, targeted amplicon sequencing, and/or RNA-sequencing of 46 pediatric primary MDS patients. Our data show that, in contrast to adult MDS, Ras/MAPK pathway mutations are common in pediatric MDS (45% of primary cohort), while mutations in RNA splicing genes are rare (2% of primary cohort). Surprisingly, germline variants in SAMD9 or SAMD9L were present in 17% of primary MDS patients, and these variants were routinely lost in the tumor cells by chromosomal deletions (e.g., monosomy 7) or copy number neutral loss of heterozygosity (CN-LOH). Our data confirm that adult and pediatric MDS are separate diseases with disparate mechanisms, and that SAMD9/SAMD9L mutations represent a new class of MDS predisposition. Myelodysplastic syndromes (MDS) are uncommon in children and have poor prognosis. Here, the authors interrogate the genomic landscape of MDS, confirming adult and paediatric MDS are separate diseases with disparate mechanisms, and highlighting that SAMD9/SAMD9L mutations represent a new class of MDS predisposition.
登录
查看更多内容
影响因子：
11.4
作者：
通讯作者：
--
影响因子：
30.8
作者：
Faber ZJ;Chen X;Gedman AL;Boggs K;Cheng J;Ma J;Radtke I;Chao JR;Walsh MP;Song G;Andersson AK;Dang J;Dong L;Liu Y;Huether R;Cai Z;Mulder H;Wu G;Edmonson M;Rusch M;Qu C;Li Y;Vadodaria B;Wang J;Hedlund E;Cao X;Yergeau D;Nakitandwe J;Pounds SB;Shurtleff S;Fulton RS;Fulton LL;Easton J;Parganas E;Pui CH;Rubnitz JE;Ding L;Mardis ER;Wilson RK;Gruber TA;Mullighan CG;Schlenk RF;Paschka P;Döhner K;Döhner H;Bullinger L;Zhang J;Klco JM;Downing JR
通讯作者：
Downing JR
RRAS 的激活突变是 RAS 病谱中表型的基础，并有助于白血病的发生。
影响因子：
3.5
作者：
Flex E;Jaiswal M;Pantaleoni F;Martinelli S;Strullu M;Fansa EK;Caye A;De Luca A;Lepri F;Dvorsky R;Pannone L;Paolacci S;Zhang SC;Fodale V;Bocchinfuso G;Rossi C;Burkitt-Wright EM;Farrotti A;Stellacci E;Cecchetti S;Ferese R;Bottero L;Castro S;Fenneteau O;Brethon B;Sanchez M;Roberts AE;Yntema HG;Van Der Burgt I;Cianci P;Bondeson ML;Cristina Digilio M;Zampino G;Kerr B;Aoki Y;Loh ML;Palleschi A;Di Schiavi E;Carè A;Selicorni A;Dallapiccola B;Cirstea IC;Stella L;Zenker M;Gelb BD;Cavé H;Ahmadian MR;Tartaglia M
通讯作者：
Tartaglia M
DOI：
10.1182/asheducation-2016.1.598
发表时间：
2016-12-01
影响因子：
3
作者：
Hasle, Henrik
通讯作者：
Hasle, Henrik
DOI：
10.1172/jci91913
发表时间：
2017-05-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Buonocore F;Kühnen P;Suntharalingham JP;Del Valle I;Digweed M;Stachelscheid H;Khajavi N;Didi M;Brady AF;Blankenstein O;Procter AM;Dimitri P;Wales JKH;Ghirri P;Knöbl D;Strahm B;Erlacher M;Wlodarski MW;Chen W;Kokai GK;Anderson G;Morrogh D;Moulding DA;McKee SA;Niemeyer CM;Grüters A;Achermann JC
通讯作者：
Achermann JC