Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma

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)
2019 pre-print
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
more » ... on, 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.
doi:10.7916/d8-qx0f-xz33 fatcat:tg2wn4db7jdyfcx43hrhmiiwoa