Abstract |
Chromosome 8p11-12 is the site of a recurrent breakpoint in a myeloproliferative disorder that involves lymphoid (T- or B-cell), myeloid hyperplasia and eosinophilia, and evolves toward acute leukemia. This multilineage involvement suggests the malignant transformation of a primitive hematopoietic stem cell. In this disorder, the 8p11-12 region is associated with three different partners 6q27, 9q33, and 13q12. We describe here the molecular characterization of the t(8;13) translocation that involves the FGFR1 gene from 8p12, encoding a tyrosine kinase receptor for members of the fibroblast growth factor family, and a gene from 13q12, tentatively named FIM (Fused In Myeloproliferative disorders). FIM is related to DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1; this defines a gene family involved in different human pathologies. The two reciprocal fusion transcripts, FIM/FGFR1 and FGFR1/FIM are expressed in the malignant cells. The FIM/FGFR1 fusion protein contains the FIM putative zinc finger motifs and the catalytic domain of FGFR1. We show that it has a constitutive tyrosine kinase activity.
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Authors | C Popovici, J Adélaïde, V Ollendorff, M Chaffanet, G Guasch, M Jacrot, D Leroux, D Birnbaum, M J Pébusque |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 95
Issue 10
Pg. 5712-7
(May 12 1998)
ISSN: 0027-8424 [Print] United States |
PMID | 9576949
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- FIM protein, Antirrhinum majus
- Plant Proteins
- Receptors, Fibroblast Growth Factor
- Recombinant Fusion Proteins
- Fibroblast Growth Factors
- FGFR1 protein, human
- Fgfr1 protein, mouse
- Receptor Protein-Tyrosine Kinases
- Receptor, Fibroblast Growth Factor, Type 1
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Topics |
- 3T3 Cells
- Amino Acid Sequence
- Animals
- Base Sequence
- Catalysis
- Chromosomes, Human, Pair 8
- Fibroblast Growth Factors
(metabolism)
- Humans
- In Situ Hybridization, Fluorescence
- Introns
- Mice
- Molecular Sequence Data
- Myeloproliferative Disorders
(genetics)
- Plant Proteins
(genetics)
- Receptor Protein-Tyrosine Kinases
- Receptor, Fibroblast Growth Factor, Type 1
- Receptors, Fibroblast Growth Factor
(genetics)
- Recombinant Fusion Proteins
(genetics)
- Sequence Alignment
- Translocation, Genetic
- Tumor Cells, Cultured
- Zinc Fingers
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