title: The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1.
abstract: We have investigated two patients with acquired chromosomal rearrangements, a male presenting with a t(1;9)(p34;q34) and B cell progenitor acute lymphoid leukemia and a female presenting with a t(8;12)(p11;q15) and the 8p11 myeloproliferative syndrome. We determined that the t(1;9) fused ABL to SFPQ (also known as PSF), a gene mapping to 1p34 that encodes a polypyrimidine tract-binding protein-associated splicing factor. The t(8;12) fused CPSF6, a cleavage and polyadenylation specificity factor, to FGFR1. The fusions were confirmed by amplification of the genomic breakpoints and RT-PCR. The predicted oncogenic products of these fusions, SFPQ-ABL and CPSF6-FGFR1, are in-frame and encode the N-terminal domain of the partner protein and the entire tyrosine kinase domain and C-terminal sequences of ABL and FGFR1. SFPQ interacts with two FGFR1 fusion partners, ZNF198 and CPSF6, that are functionally related to the recurrent PDGFRalpha partner FIP1L1. Our findings thus identify a group of proteins that are important for pre-mRNA processing as fusion partners for tyrosine kinases in hematological malignancies.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Hidalgo-Curtis
authors.forename: Andrew
authors.initials: A
authors.lastname: Chase
authors.forename: Milton
authors.initials: M
authors.lastname: Drachenberg
authors.forename: Mark W
authors.initials: MW
authors.lastname: Roberts
authors.forename: Jerry Z
authors.initials: JZ
authors.lastname: Finkelstein
authors.forename: Sarah
authors.initials: S
authors.lastname: Mould
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Francis H
authors.initials: FH
authors.lastname: Grand
mesh_terms: D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D002899:Chromosomes, Human, Pair 9; D017931:DNA Primers; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D016374:Oncogene Proteins v-abl / Q000235:genetics*; D000072670:PTB-Associated Splicing Factor; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D016374:Oncogene Proteins v-abl; D000072670:PTB-Associated Splicing Factor; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1