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

Overview

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.

authors

publication date

  • April 13, 2015

Research

keywords

  • Gene Expression Regulation, Neoplastic
  • Lymphoma, Large-Cell, Anaplastic
  • STAT3 Transcription Factor

Identity

PubMed Central ID

  • PMC5898430

Scopus Document Identifier

  • 84928015700

Digital Object Identifier (DOI)

  • 10.1038/leu.2014.347

PubMed ID

  • 25873174

Additional Document Info

volume

  • 27

issue

  • 4