Dimerization of FGFR2 ligand-independent mutants

Stable Identifier
R-HSA-2029983
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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Dimerization of FGFR2 ligand-independent mutants
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Point mutations in FGFR2 that are thought to promote ligand-independent dimerization in the context of autosomal bone development disorders have also been identified in endometrial, ovarian, gastric and lung cancer (Greenman, 2007; Dutt, 2008; Davies, 2005; Byron, 2008; Byron, 2010, Pollock, 2007). Although functional studies on these mutations in FGFR2 in cancer cell lines is limited - only the S267P mutation identified in gastric cancer has been demonstrated biochemically to undergo ligand-independent dimerization (Anderson, 1998) - characterization of paralogous mutations in FGFR3 as well as in other mutations that create unpaired cysteine residues in FGFR2 support the notion that these mutant receptors undergo aberrant intermolecular disulphide bond formation that results in constitutive activation (Galvin, 1996; Neilson and Friesel,1995; Robertson, 1998; d'Avis, 1998)
Literature References
PubMed ID Title Journal Year
17344846 Patterns of somatic mutation in human cancer genomes

Easton, DF, Dicks, E, Stratton, MR, Davies, H, Louis, DN, Tofts, C, Teh, BT, Edkins, S, Teague, J, Futreal, PA, Forbes, S, Vastrik, I, Varian, J, Wooster, R, Birney, E, Gray, K, Jones, D, Hinton, J, Hunter, C, Schmidt, EE, Yates, A, Greenman, C, Halliday, K, Yuen, ST, Hills, K, O'Meara, S, Khoo, SK, Green, AR, Jenkinson, A, Greaves, MF, Perry, J, Menzies, A, DeFazio, A, Nicholson, AG, Clements, J, Dalgliesh, GL, Chiew, YE, Choudhury, B, Chenevix-Trench, G, Harrison, R, Campbell, P, Cahill, DP, Leung, SY, Bhamra, G, Butler, A, Stephens, P, Stevens, C, Cole, J, Small, A, Brasseur, F, Smith, R, Buck, G, Raine, K, Barthorpe, S, Shepherd, R, Bignell, G, Webb, T, Tan, MH, Mironenko, T, Richardson, D, Avis, T, Looijenga, L, Weber, BL, West, S, Widaa, S, Goldstraw, P

Nature 2007
18757403 Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation

Pollock, PM, Wellens, CL, Goodfellow, PJ, Gartside, MG, Mallon, MA, Powell, MA, Byron, SA, Keenan, JB

Cancer Res 2008
17525745 Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Futreal, PA, Pollock, PM, Goodfellow, PJ, Gartside, MG, Stratton, MR, Davies, H, Mallon, MA, Mohammadi, M, Dejeza, LC, Powell, MA, Trent, JM

Oncogene 2007
9539778 Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain

Galvin, BD, Donoghue, DJ, Hart, KC, Robertson, SC, Webster, MK, Meyer, AN

Proc Natl Acad Sci U S A 1998
16140923 Somatic mutations of the protein kinase gene family in human lung cancer

Easton, DF, Dicks, E, Stratton, MR, Davies, H, Cooper, CS, Tofts, C, Teh, BT, Edkins, S, Teague, J, Pierotti, MA, Futreal, PA, Webb, A, Forbes, S, Flanagan, AM, Kosmidou, V, Lakhani, SR, Laman, R, Jones, D, Knowles, M, Hinton, J, Hunter, C, Yates, A, Greenman, C, Halliday, K, Yuen, ST, Hills, K, O'Meara, S, Perry, J, Malkowicz, B, Menzies, A, Parker, A, Nicholson, AG, Clements, J, Edwards, K, Green, A, Looijenga, LH, Harrison, R, Lugg, R, Leung, SY, Butler, A, Stephens, P, Stephens, Y, Stevens, C, Cole, J, Brackenbury, L, Small, A, Brasseur, F, Smith, R, Buck, G, Solomon, H, Raine, K, Barthorpe, S, Shepherd, R, Bignell, G, Petty, R, Avis, T, Weber, BL, West, S, Widaa, S, Goldstraw, P, Gorton, M, Gray, K, Wooster, R, Varian, J

Cancer Res 2005
9700203 Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand

Anderson, J, Enriquez-Harris, P, Heath, JK, Burns, HD, Wilkie, AO

Hum Mol Genet 1998
8755573 Constitutive receptor activation by Crouzon syndrome mutations in fibroblast growth factor receptor (FGFR)2 and FGFR2/Neu chimeras

Galvin, BD, Donoghue, DJ, Hart, KC, Webster, MK, Meyer, AN

Proc Natl Acad Sci U S A 1996
9438390 Constitutive activation of fibroblast growth factor receptor 3 by mutations responsible for the lethal skeletal dysplasia thanatophoric dysplasia type I

Bardwell, WM, Donoghue, DJ, d'Avis, PY, Robertson, SC, Webster, MK, Meyer, AN

Cell Growth Differ 1998
18552176 Drug-sensitive FGFR2 mutations in endometrial carcinoma

Akslen, LA, Cibulskis, K, Greulich, H, Dutt, A, Sellers, WR, Chen, TH, Winckler, W, Wyhs, N, Ziaugra, L, Zody, MC, Salvesen, HB, Meyerson, M, Stefansson, IM, Trovik, J, Wong, KK, Ramos, AH, Richter, DJ, Gabriel, S, Nicoletti, R, Onofrio, RC, Grewal, R, Hanna, M, Hatton, C, Engelsen, IB, Fennell, T

Proc Natl Acad Sci U S A 2008
8798788 Ligand-independent activation of fibroblast growth factor receptors by point mutations in the extracellular, transmembrane, and kinase domains

Friesel, R, Neilson, KM

J Biol Chem 1996
20106510 FGFR2 mutations are rare across histologic subtypes of ovarian cancer

Pollock, PM, Wellens, CL, Campbell, IG, Goodfellow, PJ, Gartside, MG, Birrer, MJ, Byron, SA

Gynecol Oncol 2010
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Gain of function of FGFR2 ligand-independent mutants [plasma membrane]

Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2012-01-05)
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