Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome

Genes Chromosomes Cancer. 2004 May;40(1):78-83. doi: 10.1002/gcc.20023.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence / genetics
  • Animals
  • Anopheles / genetics
  • Base Sequence / genetics
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 8 / genetics*
  • Drosophila Proteins / genetics
  • Humans
  • Insect Proteins / genetics
  • Male
  • Mice
  • Molecular Sequence Data
  • Myeloproliferative Disorders / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Rats
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / genetics*
  • Sequence Alignment / methods
  • Translocation, Genetic / genetics
  • Xenopus Proteins / genetics

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Oncogene Proteins, Fusion
  • Receptors, Fibroblast Growth Factor
  • Xenopus Proteins
  • FGFR1 protein, human
  • Fgfr1 protein, mouse
  • Fgfr1 protein, rat
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1