Novel TRAF1‐ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma. Issue 11 (2nd September 2013)

• Record Type: Journal Article
• Authors: Feldman, Andrew L.; Vasmatzis, George; Asmann, Yan W.; Davila, Jaime; Middha, Sumit; Eckloff, Bruce W.; Johnson, Sarah H.; Porcher, Julie C.; Ansell, Stephen M.; Caride, Ariel
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 11(2013:Nov.)
• Page Start: 1097
• Page End: 1102
• Publication Date: 2013-09-02
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22104
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 (<italic>ALK</italic>) gene leading to ALK fusion proteins originally were discovered in anaplastic large cell lymphomas (ALCLs). Among ALCLs, <italic>NPM1‐ALK</italic> 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‐<italic>NPM1</italic> fusion partner. We performed deep RNA sequencing of tumor tissue from this patient and identified a novel transcript fusing Exon 6 of <italic>TRAF1</italic> to Exon 20 of <italic>ALK</italic>. The <italic>TRAF1‐ALK</italic> fusion transcript was confirmed at the mRNA level by Sanger sequencing and the fusion protein was visualized by Western blot. The discovery of this <italic>TRAF1‐ALK</italic> fusion expands the diversity of known <italic>ALK</italic> fusion partners and highlights the power of deep sequencing for fusion transcript discovery. © 2013 Wiley Periodicals, Inc.</p> </abstract>