title: Novel TRAF1-ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma.
abstract: Chromosomal translocations leading to expression of abnormal fusion proteins play a major role in the pathogenesis of various hematologic malignancies. The recent development of high-throughput, "deep" sequencing has allowed discovery of novel translocations leading to a rapid increase in understanding these diseases. Translocations involving the anaplastic lymphoma kinase (ALK) gene leading to ALK fusion proteins originally were discovered in anaplastic large cell lymphomas (ALCLs). Among ALCLs, NPM1-ALK fusions are most common and lead to nuclear localization of the fusion protein. Here, we present a 50-year-old male with ALCL demonstrating cytoplasmic ALK immunoreactivity only, suggesting the presence of a non-NPM1 fusion partner. We performed deep RNA sequencing of tumor tissue from this patient and identified a novel transcript fusing Exon 6 of TRAF1 to Exon 20 of ALK. The TRAF1-ALK fusion transcript was confirmed at the mRNA level by Sanger sequencing and the fusion protein was visualized by Western blot. The discovery of this TRAF1-ALK fusion expands the diversity of known ALK fusion partners and highlights the power of deep sequencing for fusion transcript discovery. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Jaime
authors.initials: J
authors.lastname: Davila
authors.forename: Sumit
authors.initials: S
authors.lastname: Middha
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Eckloff
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Johnson
authors.forename: Julie C
authors.initials: JC
authors.lastname: Porcher
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Ariel
authors.initials: A
authors.lastname: Caride
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D050939:Gene Fusion; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017423:Sequence Analysis, RNA; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C000716967:NPM1 protein, human; D047990:TNF Receptor-Associated Factor 1; D000090243:Nucleophosmin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases