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Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma
release_tg2wn4db7jdyfcx43hrhmiiwoa
by
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,
Murty V. Vundavalli,
Angela Kadenhe-Chiweshe,
Eileen Patricia Connolly,
Andrew L. Kung
(+1 others)
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by Columbia University.
2019
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.
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