Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.
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.
Grand
Effie K
EK
Wessex Regional Genetics Laboratory, Salisbury, UK.
Grand
Francis H
FH
Chase
Andrew J
AJ
Ross
Fiona M
FM
Corcoran
Martin M
MM
Oscier
David G
DG
Cross
Nicholas C P
NC
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
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