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 l east 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 fusio n between FGFR1 and the CEP110 gene, which codes for a novel centrosome-ass ociated protein with a unique cell-cycle distribution. CEP110 is widely exp ressed 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 tyrosi ne kinase of circa 150-kd, which retains most of CEP110 with the leucine zi pper 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. (C) 2000 by The American Society of H ematology.