Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.
Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.
复制标题
DOI：
10.1016/j.ccell.2015.03.006
复制
发表时间：
2015-04-13
期刊：
影响因子：
50.3
通讯作者：
European T-Cell Lymphoma Study Group, T-Cell Project: Prospective Collection of Data in Patients with Peripheral T-Cell Lymphoma and the AIRC 5xMille Consortium “Genetics-Driven Targeted Management of Lymphoid Malignancies”
中科院分区：
文献类型：
--
作者：
Crescenzo R;Abate F;Lasorsa E;Tabbo' F;Gaudiano M;Chiesa N;Di Giacomo F;Spaccarotella E;Barbarossa L;Ercole E;Todaro M;Boi M;Acquaviva A;Ficarra E;Novero D;Rinaldi A;Tousseyn T;Rosenwald A;Kenner L;Cerroni L;Tzankov A;Ponzoni M;Paulli M;Weisenburger D;Chan WC;Iqbal J;Piris MA;Zamo' A;Ciardullo C;Rossi D;Gaidano G;Pileri S;Tiacci E;Falini B;Shultz LD;Mevellec L;Vialard JE;Piva R;Bertoni F;Rabadan R;Inghirami G;European T-Cell Lymphoma Study Group, T-Cell Project: Prospective Collection of Data in Patients with Peripheral T-Cell Lymphoma and the AIRC 5xMille Consortium “Genetics-Driven Targeted Management of Lymphoid Malignancies”
尚未对驱动alcl的遗传改变进行系统的表征。通过整合大量测序策略，我们提供了ALK - alcl中驱动基因改变（体细胞点突变，拷贝数改变和基因融合）的全面表征。我们在155例ALK - alcl中鉴定出约20%的JAK1和/或STAT3基因激活突变，并证明38%的全身性ALK - alcl表现出双重病变。在WT JAK1/STAT3 ALK−ALCL中也发现了结合转录因子（NFkB2或NCOR2）和酪氨酸激酶（ROS1或TYK2）的反复嵌合体。所有这些异常导致JAK/STAT3通路的组成性激活，这被证明是致癌的。同样，JAK/STAT3通路抑制也会损害细胞在体内和体外的生长。
A systematic characterization of the genetic alterations driving ALCLs has not been performed. By integrating massive sequencing strategies, we provide a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK− ALCLs. We identified activating mutations of JAK1 and/or STAT3 genes in ∼20% of 155 ALK− ALCLs and demonstrated that 38% of systemic ALK− ALCLs displayed double lesions. Recurrent chimeras combining a transcription factor (NFkB2 or NCOR2) with a tyrosine kinase (ROS1 or TYK2) were also discovered in WT JAK1/STAT3 ALK− ALCL. All these aberrations lead to the constitutive activation of the JAK/STAT3 pathway, which was proved oncogenic. Consistently, JAK/STAT3 pathway inhibition impaired cell growth in vitro and in vivo.
登录
查看更多内容
影响因子：
82.9
作者：
Chiarle, R;Simmons, WJ;Inghirami, G
通讯作者：
Inghirami, G
影响因子：
30.8
作者：
Palomero, Teresa;Couronne, Lucile;Khiabanian, Hossein;Kim, Mi-Yeon;Ambesi-Impiombato, Alberto;Perez-Garcia, Arianne;Carpenter, Zachary;Abate, Francesco;Allegretta, Maddalena;Haydu, J. Erika;Jiang, Xiaoyu;Lossos, Izidore S.;Nicolas, Concha;Balbin, Milagros;Bastard, Christian;Bhagat, Govind;Piris, Miguel A.;Campo, Elias;Bernard, Olivier A.;Rabadan, Raul;Ferrando, Adolfo A.
通讯作者：
Ferrando, Adolfo A.
DOI：
10.1038/nrc3612
发表时间：
2013-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4161/jkst.23828
发表时间：
2013-04-01
期刊：
JAK-STAT
影响因子：
--
作者：
Bournazou E;Bromberg J
通讯作者：
Bromberg J
DOI：
10.1073/pnas.1401180111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Lupardus, Patrick J.;Ultsch, Mark;Eigenbrot, Charles
通讯作者：
Eigenbrot, Charles