Signaling by FGFR2 in disease

Stable Identifier
Homo sapiens
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The FGFR2 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in the germline or arise somatically. Activating FGFR2 mutations in the germline give rise to a range of craniosynostotic conditions including Pfeiffer, Apert, Jackson-Weiss, Crouzon and Beare-Stevensen Cutis Gyrata syndromes. These autosomal dominant skeletal disorders are characterized by premature fusion of several sutures in the skull, and in some cases also involve syndactyly (abnormal bone fusions in the hands and feet) (reviewed in Webster and Donoghue, 1997; Burke, 1998; Cunningham, 2007).

Activating FGFR2 mutations arising somatically have been linked to the development of gastric and endometrial cancers (reviewed in Greulich and Pollock, 2011; Wesche, 2011). Many of these mutations are similar or identical to those that contribute to the autosomal disorders described above. Notably, loss-of-function mutations in FGFR2 have also been recently described in melanoma (Gartside, 2009). FGFR2 may also contribute to tumorigenesis through overexpression, as FGFR2 has been identified as a target of gene amplification in gastric and breast cancers (Kunii, 2008; Takeda, 2007).
Literature References
PubMed ID Title Journal Year
17505008 AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor

Fukuoka, K, Yamada, Y, Yanagihara, K, Nishio, K, Sasaki, H, Kimura, H, Takeda, M, Tamura, T, Komatsu, T, Yokote, H, Arao, T, Saijo, N

Clin Cancer Res 2007
21367659 Targeting mutant fibroblast growth factor receptors in cancer

Pollock, PM, Greulich, H

Trends Mol Med 2011
9154000 FGFR activation in skeletal disorders: too much of a good thing

Donoghue, DJ, Webster, MK

Trends Genet 1997
17552943 Syndromic craniosynostosis: from history to hydrogen bonds

Cunningham, ML, Heike, CL, Seto, ML, Hing, AV, Ratisoontorn, C

Orthod Craniofac Res 2007
9538690 Fibroblast growth factor receptors: lessons from the genes

Burke, D, Malcolm, S, Blundell, TL, Wilkes, D

Trends Biochem Sci 1998
19147536 Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma

Pollock, PM, Eliseenkova, AV, Wellens, CL, Curtis, AV, Gartside, MG, Bastian, BC, Byron, SA, Bengston, A, Riedesel, E, Mann, GJ, Harper, UL, Yudt, LM, Hyder, P, Chen, H, Mohammadi, M, Meltzer, PS, Ibrahimi, OA, Ma, J, Trent, JM, Curtin, JA

Mol Cancer Res 2009
21711248 Fibroblast growth factors and their receptors in cancer

Haglund, K, Wesche, J, Haugsten, EM

Biochem J 2011
18381441 FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival

Kunii, K, Gorenstein, J, Hatch, H, Lutterbach, B, Yashiro, M, Davis, L, Di Bacco, A, Elbi, C

Cancer Res 2008
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
bone development disease DOID:0080006
Cross References
BioModels Database
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