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: D Smedley, R Hamoudi, J Clark, W Warren, M Abdul-Rauf, G Somers, D Venter, K Fagan, C Cooper, J Shipley
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 7 Issue 4 Pg. 637-42 (Apr 1998) ISSN: 0964-6906 [Print] England
• PMID: 9499416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• DNA-Binding Proteins
• Receptors, Fibroblast Growth Factor
• Transcription Factors
• ZMYM2 protein, human
• Fibroblast Growth Factors
• FGFR1 protein, human
• Protein-Tyrosine Kinases
• Receptor Protein-Tyrosine Kinases
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• Amino Acid Sequence
• Artificial Gene Fusion
• Base Sequence
• Binding Sites
• Blotting, Southern
• Carrier Proteins (genetics)
• Chromosomes, Human, Pair 13
• Chromosomes, Human, Pair 8
• DNA-Binding Proteins
• Fibroblast Growth Factors (genetics)
• Humans
• In Situ Hybridization, Fluorescence
• Molecular Sequence Data
• Myeloproliferative Disorders (genetics)
• Polymerase Chain Reaction
• Protein-Tyrosine Kinases (genetics)
• Receptor Protein-Tyrosine Kinases
• Receptor, Fibroblast Growth Factor, Type 1
• Receptors, Fibroblast Growth Factor (genetics)
• Transcription Factors
• Transcription, Genetic
• Translocation, Genetic