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Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1381-1389
The t(6;8)(q27;p11) Translocation in a Stem Cell Myeloproliferative
Disorder Fuses a Novel Gene, FOP, to Fibroblast Growth
Factor Receptor 1
Cornel Popovici,
Bin Zhang,
Marie-José Grégoire,
Philippe Jonveaux,
Marina Lafage-Pochitaloff,
Daniel Birnbaum, and
Marie-Josèphe Pébusque
From the Laboratoire d'Oncologie Moléculaire, U.119 INSERM,
Institut de Cancérologie et d'Immunologie de Marseille,
Marseille, France; the Laboratoire de Biologie des Tumeurs, Institut
Paoli-Calmettes (IPC), Marseille, France; the Laboratoire de
Génétique, Centre Hospitalier Universitaire, Nancy, France;
and the Laboratoire de Cytogénétique, Département
d'Hématologie, IPC, Marseille, France.
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
(FGFR1 Oncogene 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.
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