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
Claire Hidalgo-Curtis
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Search for more papers by this authorAndrew Chase
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Search for more papers by this authorMilton Drachenberg
Long Beach Memorial Medical Center, California, CA 90801
Search for more papers by this authorMark W. Roberts
Long Beach Memorial Medical Center, California, CA 90801
Search for more papers by this authorJerry Z. Finkelstein
Long Beach Memorial Medical Center, California, CA 90801
Search for more papers by this authorSarah Mould
Department of Hematology, Royal Bournemouth Hospital, Bournemouth, UK
Search for more papers by this authorDavid Oscier
Department of Hematology, Royal Bournemouth Hospital, Bournemouth, UK
Search for more papers by this authorNicholas C. P. Cross
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Search for more papers by this authorCorresponding Author
Francis H. Grand
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UKSearch for more papers by this authorClaire Hidalgo-Curtis
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Search for more papers by this authorAndrew Chase
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Search for more papers by this authorMilton Drachenberg
Long Beach Memorial Medical Center, California, CA 90801
Search for more papers by this authorMark W. Roberts
Long Beach Memorial Medical Center, California, CA 90801
Search for more papers by this authorJerry Z. Finkelstein
Long Beach Memorial Medical Center, California, CA 90801
Search for more papers by this authorSarah Mould
Department of Hematology, Royal Bournemouth Hospital, Bournemouth, UK
Search for more papers by this authorDavid Oscier
Department of Hematology, Royal Bournemouth Hospital, Bournemouth, UK
Search for more papers by this authorNicholas C. P. Cross
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Search for more papers by this authorCorresponding Author
Francis H. Grand
Wessex Regional Genetics Laboratory, Salisbury District Hospital and Human Genetics Division, University of Southampton, Southampton, United Kingdom
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UKSearch for more papers by this authorAbstract
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 PDGFRα 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. © 2008 Wiley-Liss, Inc.
REFERENCES
- Belloni E,Trubia M,Gasparini P,Micucci C,Tapinassi C,Confalonieri S,Nuciforo P,Martino B,Lo-Coco F,Pelicci PG,Di Fiore PP. 2005. 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes. Genes Chromosomes Cancer 42: 320–325.
- Baxter EJ,Hochhaus A,Bolufer P,Reiter A,Fernandez JM,Senent L,Cervera J,Moscardo F,Sanz MA,Cross NC. 2002. The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA. Hum Mol Genet 11: 1391–1397.
- Charest A,Kheifets V,Park J,Lane K,McMahon K,Nutt CL,Housman D. Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma. 2003. Proc Natl Acad Sci USA 100: 916–921.
-
Chase A,Grand F,Zhang JG,Blackett N,Goldman J,Gordon M.
1997.
Factors influencing the false positive and negative rates of BCR-ABL fluorescence in situ hybridization.
Genes Chromosomes Cancer
18:
246–253.
10.1002/(SICI)1098-2264(199704)18:4<246::AID-GCC2>3.0.CO;2-0 CAS PubMed Web of Science® Google Scholar
- Cools J,DeAngelo DJ,Gotlib J,Stover EH,Legare RD,Cortes J,Kutok J,Clark J,Galinsky I,Griffin JD,Cross NC,Tefferi A,Malone J,Alam R,Schrier SL,Schmid J,Rose M,Vandenberghe P,Verhoef G,Boogaerts M,Wlodarska I,Kantarjian H,Marynen P,Coutre SE,Stone R,Gilliland DG. 2003. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348: 1201–1214.
- Crockett DK,Lin Z,Elenitoba-Johnson KS,Lim MS. 2004. Identification of NPM-ALK interacting proteins by tandem mass spectrometry. Oncogene 23: 2617–2629.
- Cross NCP,Reiter A. 2006. BCR-ABL negative chronic myeloid leukaemia. In: JV Melo, JM Goldman, editors. Hematologic Malignancies: Myeloproliferative disorders. New York: Springer, pp. 219–234.
- Dettwiler S,Aringhier C,Cardinale S,Keller W,Barabino SM. 2004. Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein–protein interactions, and subcellular localization. J Biol Chem 279: 35788–35797.
- De Keersmaecker K,Graux C,Odero MD,Mentens N,Somers R,Maertens J,Wlodarska I,Vandenberghe P,Hagemeijer A,Marynen P,Cools J. 2005. Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32). Blood 105: 4849–4852.
- Delaval B,Letard S,Lelievre H,Chevrier V,Daviet L,Dubreuil P,Birnbaum D. 2005. Oncogenic tyrosine kinase of malignant hemopathy targets the centrosome. Cancer Res 65: 7231–7240.
- Demiroglu A,Steer EJ,Heath C,Taylor K,Bentley M,Allen SL,Koduru P,Brody JP,Hawson G,Rodwell R,Doody ML,Carnicero F,Reiter A,Goldman JM,Melo JV,Cross NC. 2001. The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: Transforming activity and specific inhibition of FGFR1 fusion proteins. Blood 98: 3778–3783.
- Galietta A,Gunby RH,Redaelli S,Stano P,Carniti C,Bachi A,Tucker PW,Tartari CJ,Huang CJ,Colombo E,Pulford K,Puttini M,Piazza RG,Ruchatz H,Villa A,Donella-Deana A,Marin O,Perrotti D,Gambacorti-Passerini C. 2007. NPM/ALK binds and phosphorylates the RNA/DNA binding protein PSF in anaplastic large cell lymphoma. Blood 110: 2600–2609.
- Golub TR. 1997. TEL gene rearrangements in myeloid malignancy. Hematol Oncol Clin North Am 11: 1207–1220.
- Grand EK,Grand FH,Chase AJ,Ross FM,Corcoran MM,Oscier DG,Cross NC. 2004. Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome. Genes Chromosomes Cancer 40: 78–83.
- Graux C,Cools J,Melotte C,Quentmeier H,Ferrando A,Levine R,Vermeesch JR,Stul M,Dutta B,Boeckx N,Bosly A,Heimann P,Uyttebroeck A,Mentens N,Somers R,MacLeod RA,Drexler HG,Look AT,Gilliland DG,Michaux L,Vandenberghe P,Wlodarska I,Marynen P,Hagemeijer A. 2004. Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet 36: 1084–1089.
- Groffen J,Stephenson JR,Heisterkamp N,de Klein A,Bartram CR,Grosveld G. 1984. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36: 93–99.
- Guasch G,Mack GJ,Popovici C,Dastugue N,Birnbaum D,Rattner JB,Pebusque MJ. 2000. FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33). Blood 95: 1788–1796.
- Guasch G,Popovici C,Mugneret F,Chaffanet M,Pontarotti P,Birnbaum D,Pébusque MJ. 2003. Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3). Blood 101: 286–288.
- Handa N,Kukimoto-Niino M,Akasaka R,Kishishita S,Murayama K,Terada T,Inoue M,Kigawa T,Kose S,Imamoto N,Tanaka A,Hayashizaki Y,Shirouzu M,Yokoyama S. 2006. The crystal structure of mouse Nup35 reveals atypical RNP motifs and novel homodimerization of the RRM domain. J Mol Biol 363: 114–124.
- Hoch RV,Soriano P. 2006. Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Development 133: 663–673.
- Kasyapa CS,Kunapuli P,Cowell JK. 2005. Mass spectroscopy identifies the splicing-associated proteins, PSF, hnRNP H3, hnRNP A2/B1, and TLS/FUS as interacting partners of the ZNF198 protein associated with rearrangement in myeloproliferative disease. Exp Cell Res 309: 78–85.
- Kaufmann I,Martin G,Friedlein A,Langen H,Keller W. 2004. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J 23: 616–626.
- Liang S,Lutz CS. 2006. p54nrb is a component of the snRNP-free U1A (SF-A) complex that promotes pre-mRNA cleavage during polyadenylation. RNA 12: 111–121.
- Lupas A,Van Dyke M,Stock J. 1997. Predicting coiled coils from protein sequences. Science 252: 1162–1164.
- Lutz CS,Cooke C,O'Connor JP,Kobayashi R,Alwine JC. 1998. The snRNP-free U1A (SF-A) complex(es): Identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor. RNA 4: 1493–1499.
- Popovici C,Zhang B,Gregoire MJ,Jonveaux P,Lafage-Pochitaloff M,Birnbaum D,Pebusque MJ. 1999. The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroBLAST growth factor receptor 1. Blood 93: 1381–1389.
- Preker PJ,Lingner J,Minvielle-Sebastia L,Keller W. 1995. The FIP1 gene encodes a component of a yeast pre-mRNA polyadenylation factor that directly interacts with poly(A) polymerase. Cell. 81: 379–389.
- Rappsilber J,Ryder U,Lamond AI,Mann M. 2002. Large-scale proteomic analysis of the human spliceosome. Genome Res 12: 1231–1245.
- Roumiantsev S,de Aos IE,Varticovski L,Ilaria RL,Van Etten RA. 2001. The src homology 2 domain of Bcr/Abl is required for efficient induction of chronic myeloid leukemia-like disease in mice but not for lymphoid leukemogenesis or activation of phosphatidylinositol 3-kinase. Blood 97: 4–13.
- Roumiantsev S,Krause DS,Neumann CA,Dimitri CA,Asiedu F,Cross NC,Van Etten RA. 2004. Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations. Cancer Cell 5: 287–298.
- Ruegsegger U,Blank D,Keller W. 1998. Human pre-mRNA cleavage factor I-m is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits. Mol Cell 1: 243–253.
- Shav-Tal Y,Zipori D. 2002. PSF and p54(nrb)/NonO—Multi-functional nuclear proteins. FEBS Lett 531: 109–114 (review).
- Simpson PJ,Monie TP,Szendroi A,Davydova N,Tyzack JK,Conte MR,Read CM,Cary PD,Svergun DI,Konarev PV,Curry S,Matthews S. 2004. Structure and RNA interactions of the N-terminal RRM domains of PTB. Structure 12: 1631–1643.
- Sohal J,Chase A,Mould S,Corcoran M,Oscier D,Iqbal S,Parker S,Welborn J,Harris RI,Martinelli G,Montefusco V,Sinclair P,Wilkins BS,van den Berg H,Vanstraelen D,Goldman JM,Cross NC. 2001. Identification of four new translocations involving FGFR1 in myeloid disorders. Genes Chromosomes Cancer 32: 155–163.
- Walz C,Chase A,Schoch C,Weisser A,Schlegel F,Hochhaus A,Fuchs R,Schmitt-Graff A,Hehlmann R,Cross NC,Reiter A. 2005. The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1. Leukemia 19: 1005–1009.
- Xiao S,Nalabolu SR,Aster JC,Ma J,Abruzzo L,Jaffe ES,Stone R,Weissman SM,Hudson TJ,Fletcher JA. 1998. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet 18: 84–87.
- Zhou Z,Sim J,Griffith J,Reed R. Purification and electron microscopic visualization of functional human spliceosomes. 2002. Proc Natl Acad Sci USA 99: 12203–12207.
