Dimerization of cytosolic FGFR1 fusion proteins

Stable Identifier
Reaction [transition]
Homo sapiens
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8p11 myeloproliferative syndrome (EMS) is a myeloproliferative disorder that rapidly progresses to acute myeloid leukemia if not treated (reviewed in Jackson, 2010, Knights and Cook, 2010). A characteristic feature of EMS is the presence of fusion proteins that contain the kinase domain of FGFR1 and the oligomerization domain of an unrelated protein. This is believed to promote the ligand independent dimerization and activation of the kinase domain. To date, there are 11 identified partners that form fusion proteins with FGFR1 in EMS: ZMYM2 (Xiao, 1998; Popovici, 1998; Reiter, 1998; Ollendorff, 1999; Xiao, 2000), FGFR1OP1 (Popovici, 1999), CNTRL (Guasch, 2000), BCR (Demiroglu, 2001), FGFR1OP2 (Grand, 2004), TRIM24 (Belloni, 2005), CUX1 (Wasag, 2011), MYO18A (Walz, 2005), CPSF6 (Hidalgo-Curtis, 2008), HERV-K (Guasch, 2003) and LRRFIP1 (Soler, 2009).

Literature References
PubMed ID Title Journal Year
9425908 FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome

Hudson, TJ, Weissman, SM, Abruzzo, L, Nalabolu, SR, Xiao, S, Stone, R, Fletcher, JA, Aster, JC, Ma, J, Jaffe, ES

Nat Genet 1998
19874848 De-regulated FGF receptors as therapeutic targets in cancer

Cook, SJ, Knights, V

Pharmacol Ther 2010
12393597 Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3)

Pontarotti, P, Mugneret, F, Guasch, G, Chaffanet, M, Birnbaum, D, Pébusque, MJ, Popovici, C

Blood 2003
9716603 Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome

Aguiar, RC, Hernandez, JM, Sohal, J, Gonçalves, C, Macdonald, DH, Goldman, JM, Reiter, A, Cross, NC, Jennings, BA, Chase, A, Kulkarni, S

Blood 1998
10887137 ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain

Xiao, S, McCarthy, JG, Fletcher, JA, Aster, JC

Blood 2000
15800673 The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1

Fuchs, R, Weisser, A, Walz, C, Reiter, A, Schoch, C, Schmitt-Gräff, A, Schlegel, F, Cross, NC, Chase, A, Hochhaus, A, Hehlmann, R

Leukemia 2005
10688839 FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33)

Guasch, G, Mack, GJ, Birnbaum, D, Dastugue, N, Pébusque, MJ, Rattner, JB, Popovici, C

Blood 2000
10480903 Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation

Guasch, G, Galindo, R, Isnardon, D, Birnbaum, D, Pébusque, MJ, Ollendorff, V

J Biol Chem 1999
15034873 Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome

Grand, FH, Grand, EK, Corcoran, MM, Chase, AJ, Cross, NC, Ross, FM, Oscier, DG

Genes Chromosomes Cancer 2004
9949182 The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1

Grégoire, MJ, Lafage-Pochitaloff, M, Zhang, B, Birnbaum, D, Jonveaux, P, Pébusque, MJ, Popovici, C

Blood 1999
19369959 LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome

Varet, B, Soler, G, Vekemans, M, Macintyre, EA, Romana, SP, Radford-Weiss, I, Nusbaum, S

Leukemia 2009
15609342 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes

Di Fiore, PP, Gasparini, P, Belloni, E, Trubia, M, Tapinassi, C, Nuciforo, P, Micucci, C, Martino, B, Pelicci, PG, Confalonieri, S, Lo-Coco, F

Genes Chromosomes Cancer 2005
11739186 The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins

Doody, ML, Demiroglu, A, Carnicero, F, Brody, JP, Melo, JV, Koduru, P, Cross, NC, Heath, C, Hawson, G, Taylor, K, Steer, EJ, Goldman, JM, Reiter, A, Rodwell, R, Bentley, M, Allen, SL

Blood 2001
20226962 8p11 myeloproliferative syndrome: a review

Jackson, CC, Medeiros, LJ, Miranda, RN

Hum Pathol 2010
9576949 Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13)

Leroux, D, Jacrot, M, Guasch, G, Chaffanet, M, Adelaide, J, Birnbaum, D, Pébusque, MJ, Popovici, C, Ollendorff, V

Proc Natl Acad Sci U S A 1998
18205209 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

Grand, FH, Hidalgo-Curtis, C, Finkelstein, JZ, Drachenberg, M, Roberts, MW, Cross, NC, Oscier, D, Chase, A, Mould, S

Genes Chromosomes Cancer 2008
21330321 The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11)

Wasag, B, Vandenberghe, P, Meeus, P, Lierman, E, Cools, J

Haematologica 2011
Functional status

Gain of function of cytosolic FGFR1 fusion mutants [cytosol]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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