| Literature DB >> 25873174 |
Ramona Crescenzo1, Francesco Abate2, Elena Lasorsa3, Fabrizio Tabbo'1, Marcello Gaudiano1, Nicoletta Chiesa3, Filomena Di Giacomo3, Elisa Spaccarotella3, Luigi Barbarossa3, Elisabetta Ercole3, Maria Todaro1, Michela Boi1, Andrea Acquaviva4, Elisa Ficarra4, Domenico Novero5, Andrea Rinaldi6, Thomas Tousseyn7, Andreas Rosenwald8, Lukas Kenner9, Lorenzo Cerroni10, Alexander Tzankov11, Maurilio Ponzoni12, Marco Paulli13, Dennis Weisenburger14, Wing C Chan14, Javeed Iqbal15, Miguel A Piris16, Alberto Zamo'17, Carmela Ciardullo18, Davide Rossi18, Gianluca Gaidano18, Stefano Pileri19, Enrico Tiacci20, Brunangelo Falini20, Leonard D Shultz21, Laurence Mevellec22, Jorge E Vialard23, Roberto Piva24, Francesco Bertoni25, Raul Rabadan26, Giorgio Inghirami27.
Abstract
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 88 [corrected] 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.Entities:
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Year: 2015 PMID： 25873174 PMCID： PMC5898430 DOI： 10.1016/j.ccell.2015.03.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743