Convergent Mutations and Kinase Fusions Lead to Oncogenic STAT3 Activation in Anaplastic Large Cell Lymphoma.
Document Type
Article
Publication Date
4-13-2015
JAX Source
Cancer Cell 2015 Apr 13; 27(4):516-32.
Volume
27
Issue
4
First Page
516
Last Page
532
ISSN
1878-3686
PMID
25873174
Grant
CA034196
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 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. Cancer Cell 2015 Apr 13; 27(4):516-32.
Recommended Citation
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 W,
Iqbal J,
Piris M,
Zamo' A,
Ciardullo C,
Rossi D,
Gaidano G,
Pileri S,
Tiacci E,
Falini B,
Shultz LD,
Mevellec L,
Vialard J,
Piva R,
Bertoni F,
Rabadan R,
Inghirami G.
Convergent Mutations and Kinase Fusions Lead to Oncogenic STAT3 Activation in Anaplastic Large Cell Lymphoma. Cancer Cell 2015 Apr 13; 27(4):516-32.