title: The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP.
abstract: A recently described atypical myeloproliferative disorder is invariably associated with reciprocal translocations involving 8p11-12. The most common rearrangement is a t(8;13)(p11;q11-12). Here we determine that this translocation results in the fusion of the fibroblast growth factor receptor 1 gene (FGFR1), a member of the receptor tyrosine kinase family at 8p11, to a novel gene at 13q11-12 designated RAMP . The predicted RAMP protein exhibits strong homology to the product of a recently cloned candidate gene for X-linked mental retardation, DXS6673E . We also provide the first report of a novel, putative metal-binding motif, present as five tandem repeats in both RAMP and DXS6673E. RT-PCR detected only one of the two possible fusion transcripts, encoding a product 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 kinases in fusion proteins in non-Hodgkin's lymphoma, chronic myelomonocytic leukaemia and papillary thyroid carcinoma described similar rearrangements. By analogy with these, we propose that the RAMP-FGFR1 fusion product will contribute to progression of this myeloproliferative disorder by constitutive activation of tyrosine kinase function.
authors.affiliation: Cell Biology and Experimental Pathology Section, Institute of Cancer Research, Haddow Laboratories, Belmont, Surrey SM2 5NG, UK. damian@icr.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Smedley
authors.forename: R
authors.initials: R
authors.lastname: Hamoudi
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: W
authors.initials: W
authors.lastname: Warren
authors.forename: M
authors.initials: M
authors.lastname: Abdul-Rauf
authors.forename: G
authors.initials: G
authors.lastname: Somers
authors.forename: D
authors.initials: D
authors.lastname: Venter
authors.forename: K
authors.initials: K
authors.lastname: Fagan
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Shipley
mesh_terms: D000595:Amino Acid Sequence; D019677:Artificial Gene Fusion; D001483:Base Sequence; D001665:Binding Sites; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins; D005346:Fibroblast Growth Factors / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; C111777:ZMYM2 protein, human; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1