FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33)

Blood. 2000 Mar 1;95(5):1788-96.

Abstract

The hallmark of the 8p12 stem cell myeloproliferative disorder (MPD) is the disruption of the FGFR1 gene, which encodes a tyrosine kinase receptor for members of the fibroblast growth factor family. FGFR1 can be fused to at least 3 partner genes at chromosomal regions 6q27, 9q33, or 13q12. We report here the cloning of the t(8;9)(p12;q33) and the detection of a novel fusion betweenFGFR1 and the CEP110 gene, which codes for a novel centrosome-associated protein with a unique cell-cycle distribution. CEP110 is widely expressed at various levels in different tissues and is predicted to encode a 994-amino acid coiled-coil protein with 4 consensus leucine zippers [L-X(6)-L-X(6)-L-X(6)-L]. Both reciprocal fusion transcripts are expressed in the patient's cells. The CEP110-FGFR1 fusion protein encodes an aberrant tyrosine kinase of circa 150-kd, which retains most of CEP110 with the leucine zipper motifs and the catalytic domain of FGFR1. Transient expression studies show that the CEP110-FGFR1 protein has a constitutive kinase activity and is located within the cell cytoplasm. (Blood. 2000;95:1788-1796)

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adult
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Cell Cycle
  • Centrosome / chemistry*
  • Chlorocebus aethiops
  • Chromosomes, Human, Pair 8 / genetics*
  • Chromosomes, Human, Pair 8 / ultrastructure
  • Chromosomes, Human, Pair 9 / genetics*
  • Chromosomes, Human, Pair 9 / ultrastructure
  • Consensus Sequence
  • DNA, Complementary / genetics
  • Disease Progression
  • Fatal Outcome
  • Gene Expression Regulation, Leukemic
  • HeLa Cells
  • Humans
  • Leucine Zippers / genetics
  • Male
  • Mice
  • Molecular Sequence Data
  • Myeloproliferative Disorders / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / immunology
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor, Fibroblast Growth Factor, Type 1
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / immunology
  • Transfection
  • Translocation, Genetic / genetics*

Substances

  • DNA, Complementary
  • Oncogene Proteins, Fusion
  • Recombinant Fusion Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • CEP110-FGFR1 fusion protein, human