title: Identification of four new translocations involving FGFR1 in myeloid disorders.
abstract: The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes (ZNF198, CEP110, and FOP, respectively) to the entire tyrosine kinase domain of FGFR1. In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT-PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two-color FISH assay using two differentially labeled PAC clones that flank FGFR1. Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph-negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T-cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98. We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two-color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1.
authors.affiliation: Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: J
authors.initials: J
authors.lastname: Sohal
authors.forename: A
authors.initials: A
authors.lastname: Chase
authors.forename: S
authors.initials: S
authors.lastname: Mould
authors.forename: M
authors.initials: M
authors.lastname: Corcoran
authors.forename: D
authors.initials: D
authors.lastname: Oscier
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.forename: S
authors.initials: S
authors.lastname: Parker
authors.forename: J
authors.initials: J
authors.lastname: Welborn
authors.forename: R I
authors.initials: RI
authors.lastname: Harris
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: V
authors.initials: V
authors.lastname: Montefusco
authors.forename: P
authors.initials: P
authors.lastname: Sinclair
authors.forename: B S
authors.initials: BS
authors.lastname: Wilkins
authors.forename: H
authors.initials: H
authors.lastname: van den Berg
authors.forename: D
authors.initials: D
authors.lastname: Vanstraelen
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: N C
authors.initials: NC
authors.lastname: Cross
mesh_terms: D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping; D008297:Male; D009196:Myeloproliferative Disorders / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1