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

• Published in: Blood 2000-03, Vol.95 (5), p.1788
• Main Authors: Guasch, G, Mack, G J, Popovici, C, Dastugue, N, Birnbaum, D, Rattner, J B, Pébusque, M J
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adult; Amino Acid Sequence; Animals; Base Sequence; 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; COS Cells; Disease Progression; DNA, Complementary - genetics; 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
• ISSN: 0006-4971
• DOI: 10.1182/blood.v95.5.1788.005k15_1788_1796

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)