THE T(8-3)(P11-Q11-12) REARRANGEMENT ASSOCIATED WITH AN ATYPICAL MYELOPROLIFERATIVE DISORDER FUSES THE FIBROBLAST GROWTH-FACTOR RECEPTOR-1 GENE TO A NOVEL GENE RAMP

A recently described atypical myeloproliferative disorder is invariabl y associated with reciprocal translocations involving 8p11-12, The mos t common rearrangement is a t(8;13)(p11;q11-12), Here we determine tha t this translocation results in the fusion of the fibroblast growth fa ctor receptor 1 gene (FGFR1), a member of the receptor tyrosine kinase family at 8p11, to a novel gene at 13q11-12 designated RAMP. The pred icted RAMP protein exhibits strong homology to the product of a recent ly cloned candidate gene for X-linked mental retardation, DXS6673E. We also provide the first report of a novel, putative metal-binding moti f, present as five tandem repeats in both RAMP and DXS6673E, RT-PCR de tected only one of the two possible fusion transcripts, encoding a pro duct in which the N-terminal 641 amino acids of RAMP become joined to the tyrosine kinase domain of FGFR1, Receptor tyrosine kinases are not commonly involved in the formation of tumour-specific fusion proteins . However, the previous reports of involvement of receptor tyrosine ki nases in fusion proteins in non-Hodgkin's lymphoma, chronic myelomonoc ytic leukaemia and papillary thyroid carcinoma described similar rearr angements, By analogy with these, we propose that the RAMP-FGFR1 fusio n product will contribute to progression of this myeloproliferative di sorder by constitutive activation of tyrosine kinase function.