title: The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.
abstract: The 8p11 myeloproliferative syndrome (EMS) also known as stem cell leukemia-lymphoma syndrome (SCLL) is associated with translocations that disrupt FGFR1. The resultant fusion proteins are constitutively active tyrosine kinases, and different FGFR1 fusions are associated with subtly different disease phenotypes. We report here a patient with a t(8;17)(p11;q23) and an unusual myelodysplastic/myeloproliferative disease (MDS/MPD) characterized by thrombocytopenia due to markedly reduced size and numbers of megakaryocytes, with elevated numbers of monocytes, eosinophils and basophils. A novel mRNA fusion between exon 32 of the myosin XVIIIA gene (MYO18A) at chromosome band 17q11 and exon 9 of FGFR1 was identified. Partial characterization of the genomic breakpoints in combination of bubble-PCR with fluorescence in situ hybridization revealed that the t(8;17) arose from a three-way translocation with breaks at 8p11, 17q11 and 17q23. MYO18A-FGFR1 is structurally similar to other fusion tyrosine kinases and is likely to be the causative transforming lesion in this unusual MDS/MPD.
authors.affiliation: III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, 68305 Mannheim, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Walz
authors.forename: A
authors.initials: A
authors.lastname: Chase
authors.forename: C
authors.initials: C
authors.lastname: Schoch
authors.forename: A
authors.initials: A
authors.lastname: Weisser
authors.forename: F
authors.initials: F
authors.lastname: Schlegel
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: R
authors.initials: R
authors.lastname: Fuchs
authors.forename: A
authors.initials: A
authors.lastname: Schmitt-Gräff
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: N C P
authors.initials: NC
authors.lastname: Cross
authors.forename: A
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001491:Basophils / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D002898:Chromosomes, Human, Pair 8; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D009218:Myosins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013921:Thrombocytopenia / Q000235:genetics / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D009218:Myosins