Open AccessFibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13)(p12;q12)
Author(s) -
Cornel Popovici,
José Adélaı̈de,
Vincent Ollendorff,
Max Chaffanet,
Géraldine Guasch,
M. Jacrot,
Dominique Leroux,
Daniel Birnbaum,
MarieJosèphe Pébusque
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.10.5712
Subject(s) - fibroblast growth factor receptor 1 , biology , fusion gene , stem cell , breakpoint , fibroblast growth factor receptor , cancer research , haematopoiesis , proto oncogene proteins c kit , fusion protein , chromosomal translocation , microbiology and biotechnology , fibroblast growth factor , genetics , gene , stem cell factor , receptor , recombinant dna
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 theFGFR1 gene from 8p12, encoding a tyrosine kinase receptor for members of the fibroblast growth factor family, and a gene from 13q12, tentatively namedFIM (F usedI nM yeloproliferative disorders).FIM is related toDXS6673E , 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 andFGFR1/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.