Characterization of a Novel Fusion Gene EML4-NTRK3 in a Case of Recurrent Congenital Fibrosarcoma

Overview

Journal Cold Spring Harb Mol Case Stud

Specialty Genetics

Date 2016 May 6

PMID 27148571

Citations 19

Authors

Sarah Tannenbaum-Dvir

Julia L Glade Bender

Alanna J Church

Katherine A Janeway

Marian H Harris

Mahesh M Mansukhani

Peter L Nagy

Stuart J Andrews

Vundavalli V Murty

Angela Kadenhe-Chiweshe

Eileen P Connolly

Andrew L Kung

Filemon S Dela Cruz

Affiliations

Soon will be listed here.

Abstract

We describe the clinical course of a recurrent case of congenital fibrosarcoma diagnosed in a 9-mo-old boy with a history of hemimelia. Following complete surgical resection of the primary tumor, the patient subsequently presented with bulky bilateral pulmonary metastases 6 mo following surgery. Molecular characterization of the tumor revealed the absence of the prototypical ETV6-NTRK3 translocation. However, tumor characterization incorporating cytogenetic, array comparative genomic hybridization, and RNA sequencing analyses, revealed a somatic t(2;15)(2p21;15q25) translocation resulting in the novel fusion of EML4 with NTRK3. Cloning and expression of EML4-NTRK3 in murine fibroblast NIH 3T3 cells revealed a potent tumorigenic phenotype as assessed in vitro and in vivo. These results demonstrate that multiple fusion partners targeting NTRK3 can contribute to the development of congenital fibrosarcoma.

Citing Articles

The oncogenic fusion protein EML4-NTRK3 requires three salt bridges for stability and biological activity.

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Functional Classification of Fusion Proteins in Sarcoma.

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Progressive insights into fibrosarcoma diagnosis and treatment: leveraging fusion genes for advancements.

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