(Cold Spring Harbor Laboratory Press, 2015) Tannenbaum-Dvir, Sarah; Glade Bender, Julia L.; Church, Alanna; Janeway, Katherine; Harris, Marian; Mansukhani, Mahesh M.; Nagy, Peter L.; Andrews, Stuart J.; Murty, Vundavalli V.; Kadenhe-Chiweshe, Angela; Connolly, Eileen P.; Kung, Andrew L.; Dela Cruz, Filemon S.
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.
