TY - JOUR
T1 - Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma
AU - The 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
AU - Crescenzo, Ramona
AU - Abate, Francesco
AU - Lasorsa, Elena
AU - Tabbo', Fabrizio
AU - Gaudiano, Marcello
AU - Chiesa, Nicoletta
AU - Di Giacomo, Filomena
AU - Spaccarotella, Elisa
AU - Barbarossa, Luigi
AU - Ercole, Elisabetta
AU - Todaro, Maria
AU - Boi, Michela
AU - Acquaviva, Andrea
AU - Ficarra, Elisa
AU - Novero, Domenico
AU - Rinaldi, Andrea
AU - Tousseyn, Thomas
AU - Rosenwald, Andreas
AU - Kenner, Lukas
AU - Cerroni, Lorenzo
AU - Tzankov, Alexander
AU - Ponzoni, Maurilio
AU - Paulli, Marco
AU - Weisenburger, Dennis
AU - Chan, Wing C.
AU - Iqbal, Javeed
AU - Piris, Miguel A.
AU - Zamo', Alberto
AU - Ciardullo, Carmela
AU - Rossi, Davide
AU - Gaidano, Gianluca
AU - Pileri, Stefano
AU - Tiacci, Enrico
AU - Falini, Brunangelo
AU - Shultz, Leonard D.
AU - Mevellec, Laurence
AU - Vialard, Jorge E.
AU - Piva, Roberto
AU - Bertoni, Francesco
AU - Rabadan, Raul
AU - Inghirami, Giorgio
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/13
Y1 - 2015/4/13
N2 - 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 invitro and invivo.
AB - 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 invitro and invivo.
UR - http://www.scopus.com/inward/record.url?scp=84928015700&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2015.03.006
DO - 10.1016/j.ccell.2015.03.006
M3 - Article
SN - 1535-6108
VL - 27
SP - 516
EP - 532
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -
