title: Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma.
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.
authors.affiliation: Columbia University Medical Center, Department of Pediatric Oncology/Hematology/Stem Cell Transplantation, Department of Pediatrics, New York, New York 10032, USA;
authors.forename: Sarah
authors.initials: S
authors.lastname: Tannenbaum-Dvir
authors.affiliation: Columbia University Medical Center, Department of Pediatric Oncology/Hematology/Stem Cell Transplantation, Department of Pediatrics, New York, New York 10032, USA;
authors.forename: Julia L
authors.initials: JL
authors.lastname: Glade Bender
authors.affiliation: Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA;
authors.forename: Alanna J
authors.initials: AJ
authors.lastname: Church
authors.affiliation: Harvard Medical School, Department of Pediatric Oncology/Hematology, Boston, Massachusetts 02115, USA;
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Janeway
authors.affiliation: Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA;
authors.forename: Marian H
authors.initials: MH
authors.lastname: Harris
authors.affiliation: Columbia University Medical Center, Department of Pathology and Cell Biology, New York, New York 10032, USA;
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Mansukhani
authors.affiliation: Columbia University Medical Center, Department of Pathology and Cell Biology, New York, New York 10032, USA;
authors.forename: Peter L
authors.initials: PL
authors.lastname: Nagy
authors.affiliation: Columbia University Medical Center, Department of Pathology and Cell Biology, New York, New York 10032, USA;
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Andrews
authors.affiliation: Columbia University Medical Center, Department of Pathology and Cell Biology, New York, New York 10032, USA;
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.affiliation: Columbia University Medical Center, Department of Surgery, New York, New York 10032, USA;
authors.forename: Angela
authors.initials: A
authors.lastname: Kadenhe-Chiweshe
authors.affiliation: Columbia University Medical Center, Department of Radiation Oncology, New York, New York 10032, USA.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Connolly
authors.affiliation: Columbia University Medical Center, Department of Pediatric Oncology/Hematology/Stem Cell Transplantation, Department of Pediatrics, New York, New York 10032, USA;
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kung
authors.affiliation: Columbia University Medical Center, Department of Pediatric Oncology/Hematology/Stem Cell Transplantation, Department of Pediatrics, New York, New York 10032, USA;
authors.forename: Filemon S
authors.initials: FS
authors.lastname: Dela Cruz
keywords: abnormality of the musculature of the limbs; congenital fibrosarcoma