Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma
- Sarah Tannenbaum-Dvir1,
- Julia L. Glade Bender1,
- Alanna J. Church2,
- Katherine A. Janeway3,
- Marian H. Harris2,
- Mahesh M. Mansukhani4,
- Peter L. Nagy4,
- Stuart J. Andrews4,
- Vundavalli V. Murty4,
- Angela Kadenhe-Chiweshe5,
- Eileen P. Connolly6,
- Andrew L. Kung1 and
- Filemon S. Dela Cruz1
- 1Columbia University Medical Center, Department of Pediatric Oncology/Hematology/Stem Cell Transplantation, Department of Pediatrics, New York, New York 10032, USA;
- 2Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA;
- 3Harvard Medical School, Department of Pediatric Oncology/Hematology, Boston, Massachusetts 02115, USA;
- 4Columbia University Medical Center, Department of Pathology and Cell Biology, New York, New York 10032, USA;
- 5Columbia University Medical Center, Department of Surgery, New York, New York 10032, USA;
- 6Columbia University Medical Center, Department of Radiation Oncology, New York, New York 10032, USA
- Corresponding authors: fd2177{at}cumc.columbia.edu, akung{at}columbia.edu
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.
- Received July 1, 2015.
- Accepted August 5, 2015.
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