The t(6;8)(q27;p11) Translocation in a Stem Cell Myeloproliferative Disorder Fuses a Novel Gene, FOP, to Fibroblast Growth Factor Receptor 1
| Autor: | Marina Lafage-Pochitaloff, Bin Zhang, Cornel Popovici, Daniel Birnbaum, Marie-José Grégoire, Philippe Jonveaux, Marie-Josèphe Pébusque |
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| Rok vydání: | 1999 |
| Předmět: |
ABL
biology T cell Fibroblast growth factor receptor 1 Immunology Chromosomal translocation Cell Biology Hematology Biochemistry Molecular biology Hematopoietic stem cell proliferation Receptor tyrosine kinase medicine.anatomical_structure Fibroblast growth factor receptor medicine biology.protein Gene |
| Zdroj: | Blood. 93:1381-1389 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v93.4.1381 |
| Popis: | In patients with an atypical stem-cell myeloproliferative disorder with lymphoma (B or T cell), myeloid hyperplasia, and eosinophilia, the chromosome 8p11-12 region is the site of a recurrent breakpoint that can be associated with three different partners, 6q27, 9q32-34, and 13q12. Rearrangements are supposed to affect a pluripotent stem cell capable of myeloid and lymphoid differentiation and to involve the same 8p11-12 gene. The t(8;13) translocation has recently been shown to result in a fusion between the FGFR1 gene that encodes a tyrosine kinase receptor for fibroblast growth factors and a novel gene, FIM (also called RAMP or ZNF198), belonging to a novel family of zinc finger genes. In the present study, we have cloned the t(6;8)(q27;p11) translocation in two patients and found a fusion between FGFR1 and a novel gene, FOP(FGFR1Oncogene Partner), located on chromosome band 6q27. This gene is alternatively spliced and ubiquitously expressed. It encodes a protein containing two regions of putative leucine-rich repeats putatively folding in -helices and separated by a hydrophobic spacer. The two reciprocal fusion transcripts were evidenced by reverse transcription-polymerase chain reaction in the tumoral cells of the patients. The predicted chimeric FOP-FGFR1 protein contains the FOP N-terminus leucine-rich region fused to the catalytic domain of FGFR1. It may promote hematopoietic stem cell proliferation and leukemogenesis through a constitutive phosphorylation and activation of the downstream pathway of FGFR1. |
| Databáze: | OpenAIRE |
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