The detection of Tel–TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma

The t(12;15)(p13;q25) translocation, a recurrent chromosomal abnormality of congenital fibrosarcoma, leads to the expression of a Tel–TrkC fusion transcript. To determine whether detection of the chimeric protein may be helpful for the diagnosis of congenital fibrosarcoma, immunohistochemistry was performed with an anti‐TrkC antibody on 26 spindle cell tumours of newborn or young children (n=19) or adults (n=7). Four out of five congenital fibrosarcomas showed TrkC immunoreactivity with cytoplasmic paranuclear staining. However, TrkC immunoreactivity was not restricted to congenital fibrosarcoma and was observed in infantile myofibromatosis, congenital haemangiopericytoma, desmoid tumour, nodular fasciitis, fibrous hamartoma, inflammatory myofibroblastic tumour, and adult fibrosarcoma. RT‐PCR analysis was performed on nine cases, including four congenital fibrosarcomas, for which frozen material was available. Tel–TrkC transcripts were detected by RT‐PCR in the four congenital fibrosarcomas analysed, but not in the five other spindle cell tumours. Furthermore, several Tel–TrkC transcripts encoding for kinase isoforms of the Tel–TrkC protein were detected in congenital fibrosarcoma and may be involved in oncogenesis. The reciprocal TrkC–Tel transcript was detected in only one congenital fibrosarcoma. While the detection of a Tel–TrkC fusion transcript is a recurrent feature of congenital fibrosarcoma, TrkC immunoreactivity does not appear specific for the diagnosis of fibromatous paediatric tumours. Copyright © 2000 John Wiley & Sons, Ltd.

[1]  K. Tanaka,et al.  Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). , 1999, Blood.

[2]  P Dubus,et al.  Expression of neurotrophins and their receptors in human bone marrow. , 1999, The American journal of pathology.

[3]  P. Sorensen,et al.  ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. , 1998, Cancer research.

[4]  J. Fletcher,et al.  Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. , 1998, The American journal of pathology.

[5]  R. González-Sarmiento,et al.  Genomic characterization of the human trkC gene , 1998, Oncogene.

[6]  K. Badizadegan,et al.  Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. , 1998, The American journal of surgical pathology.

[7]  P. Sorensen,et al.  A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma , 1998, Nature Genetics.

[8]  L. Tessarollo,et al.  Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R Berger,et al.  A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. , 1997, Science.

[10]  P. Marynen,et al.  Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. , 1997, Blood.

[11]  K. Pulford,et al.  Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. , 1997, Blood.

[12]  R. Berger,et al.  The TEL gene products: nuclear phosphoproteins with DNA binding properties , 1997, Oncogene.

[13]  T. Deerinck,et al.  Translocation of RNA Granules in Living Neurons , 1996, The Journal of Neuroscience.

[14]  T. Golub,et al.  The TEL/platelet-derived growth factor β receptor (PDGFβR) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGFβR kinase-dependent signaling pathways , 1996 .

[15]  L. Tessarollo,et al.  Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development , 1996, Nature Genetics.

[16]  T. Golub,et al.  Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia , 1996, Molecular and cellular biology.

[17]  H. Koizumi,et al.  Cellular localization of the Trk neurotrophin receptor family in human non-neuronal tissues. , 1996, The American journal of pathology.

[18]  P. Marynen,et al.  The 12;21 translocation involving TEL and deletion of the other TEL allele: two frequently associated alterations found in childhood acute lymphoblastic leukemia. , 1996, Blood.

[19]  D. Kaplan,et al.  Association of neurotrophin receptor expression and differentiation in human neuroblastoma. , 1995, The American journal of pathology.

[20]  D. Le Paslier,et al.  The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. , 1995, Blood.

[21]  P. Riegman,et al.  Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11. , 1995, Oncogene.

[22]  J. Biegel,et al.  Molecular assays for chromosomal translocations in the diagnosis of pediatric soft tissue sarcomas. , 1995, JAMA.

[23]  J. Gorp,et al.  Are infantile myofibromatosis, congenital fibrosarcoma and congenital haemangiopericytoma histogenetically related? , 1995, Histopathology.

[24]  M. Barbacid.  The Trk family of neurotrophin receptors. , 1994, Journal of neurobiology.

[25]  C. Fletcher,et al.  Infantile Hemangiopericytoma Versus Infantile Myofibromatosis Study of a Series Suggesting a Continuous Spectrum of Infantile Myofibroblastic Lesions , 1994, The American journal of surgical pathology.

[26]  S. Baylin,et al.  Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal assignment, and evidence for a splice variant. , 1994, Genomics.

[27]  Todd R. Golub,et al.  Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation , 1994, Cell.

[28]  M. Barbacid,et al.  trkC encodes multiple neurotrophin‐3 receptors with distinct biological properties and substrate specificities. , 1993, The EMBO journal.

[29]  N. Copeland,et al.  trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. , 1993, Development.

[30]  P. Ernfors,et al.  Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system , 1992, Neuroscience.

[31]  M. Barbacid,et al.  trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3 , 1991, Cell.

[32]  T. Golub,et al.  The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  L. Wiedemann,et al.  The novel activation of ABL by fusion to an ets-related gene, TEL. , 1995, Cancer research.