title: Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.
abstract: The 8p11 myeloproliferative syndrome (EMS) is an aggressive hematological malignancy caused by the fusion of diverse partner genes to fibroblast growth factor receptor 1 (FGFR1). The partner proteins promote dimerization and ligand-independent activation of FGFR1-encoded tyrosine kinase, deregulating hemopoiesis in a manner analogous to BCR-ABL in chronic myeloid leukemia. Here, we describe the identification of a new FGFR1 fusion gene in a patient who presented with T-cell lymphoblastic lymphoma in conjunction with an acquired ins(12;8)(p11;p11p22). Initial FISH analysis and Southern blotting confirmed that FGFR1 was disrupted. Using 5'-RACE PCR, we identified part of a novel gene, FGFR1OP2, at chromosome band 12p11 that was fused to exon 9 of FGFR1.FGFR1OP2 is predicted to be translated into an evolutionarily conserved protein containing coiled-coil domains but no other recognizable motifs. The presence of the chimeric gene was confirmed by RT-PCR, genomic DNA PCR, and FISH. These data further support the central role of deregulated FGFR1 in the pathogenesis of EMS.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.
authors.forename: Effie K
authors.initials: EK
authors.lastname: Grand
authors.forename: Francis H
authors.initials: FH
authors.lastname: Grand
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Chase
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
authors.forename: Martin M
authors.initials: MM
authors.lastname: Corcoran
authors.forename: David G
authors.initials: DG
authors.lastname: Oscier
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000852:Anopheles / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods; D014178:Translocation, Genetic / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D019476:Insect Proteins; D015514:Oncogene Proteins, Fusion; D017468:Receptors, Fibroblast Growth Factor; D029867:Xenopus Proteins; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1