FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).
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)
Guasch
G
G
Laboratoire d'Oncologie Moléculaire, Inserm U119, Institut de Cancérologie et d'Immunologie de Marseille, Marseille, France.
Mack
G J
GJ
Popovici
C
C
Dastugue
N
N
Birnbaum
D
D
Rattner
J B
JB
Pébusque
M J
MJ
D016475:3T3 Cells; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002453:Cell Cycle; D018385:Centrosome / Q000737:chemistry*; D002522:Chlorocebus aethiops; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics* / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics* / Q000648:ultrastructure; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D017809:Fatal Outcome; D015973:Gene Expression Regulation, Leukemic; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D051496:Receptor, Fibroblast Growth Factor, Type 1; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection; D014178:Translocation, Genetic / Q000235:genetics*
D018076:DNA, Complementary; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; C405614:CEP110-FGFR1 fusion protein, human