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

被引:93
作者
Smedley, D [1 ]
Hamoudi, R
Clark, J
Warren, W
Abdul-Rauf, M
Somers, G
Venter, D
Fagan, K
Cooper, C
Shipley, J
机构
[1] Inst Canc Res, Haddow Labs, Cell Biol & Expt Pathol Sect, Belmont SM2 5NG, Surrey, England
[2] Inst Canc Res, Haddow Labs, Canc Gene Cloning Lab, Belmont SM2 5NG, Surrey, England
[3] Inst Canc Res, Haddow Labs, Mol Carcinogenesis Sect, Belmont SM2 5NG, Surrey, England
[4] Inst Canc Res, Haddow Labs, Acad Haematol & Cytogenet Sect, Belmont SM2 5NG, Surrey, England
[5] Peter MacCallum Canc Inst, Dept Pathol, E Melbourne, Vic, Australia
[6] Mater Hosp, Hunter Area Pathol Serv, Waratah, NSW, Australia
基金
英国惠康基金;
关键词
D O I
10.1093/hmg/7.4.637
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:637 / 642
页数:6
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