title: Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13).
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.
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Unité 119, Institut National de la Santé et de la Recherche Médicale, Institut de Cancérologie et Immunologie, 232 Boulevard Sainte-Marguerite, 13009 Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Popovici
authors.forename: J
authors.initials: J
authors.lastname: Adélaïde
authors.forename: V
authors.initials: V
authors.lastname: Ollendorff
authors.forename: M
authors.initials: M
authors.lastname: Chaffanet
authors.forename: G
authors.initials: G
authors.lastname: Guasch
authors.forename: M
authors.initials: M
authors.lastname: Jacrot
authors.forename: D
authors.initials: D
authors.lastname: Leroux
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: M J
authors.initials: MJ
authors.lastname: Pébusque
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002898:Chromosomes, Human, Pair 8; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000235:genetics*; D010940:Plant Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016415:Sequence Alignment; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
chemical_list: C088434:FIM protein, Antirrhinum majus; D010940:Plant Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1