Cancer cell · 2015

Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Crescenzo Ramona, Abate Francesco, Lasorsa Elena, Tabbo' Fabrizio, Gaudiano Marcello, Chiesa Nicoletta, Di Giacomo Filomena, Spaccarotella Elisa, Barbarossa Luigi, Ercole Elisabetta, Todaro Maria, Boi Michela, Acquaviva Andrea, Ficarra Elisa, Novero Domenico, Rinaldi Andrea, Tousseyn Thomas, Rosenwald Andreas, Kenner Lukas, Cerroni Lorenzo, Tzankov Alexander, Ponzoni Maurilio, Paulli Marco, Weisenburger Dennis, Chan Wing C, Iqbal Javeed, Piris Miguel A, Zamo' Alberto, Ciardullo Carmela, Rossi Davide, Gaidano Gianluca, Pileri Stefano, Tiacci Enrico, Falini Brunangelo, Shultz Leonard D, Mevellec Laurence, Vialard Jorge E, Piva Roberto, Bertoni Francesco, Rabadan Raul, Inghirami Giorgio, 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”

Аннотация

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.

Предметные рубрики MeSH

Activating Transcription Factor 3 Animals Cell Line, Tumor Gene Expression Regulation, Neoplastic HEK293 Cells Humans Janus Kinase 1 Lymphoma, Large-Cell, Anaplastic Mice Mutant Chimeric Proteins NF-kappa B Phosphorylation Proto-Oncogene Proteins Receptor Protein-Tyrosine Kinases STAT3 Transcription Factor Signal Transduction TYK2 Kinase

Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH