Signaling by FGFR1 amplification mutants

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R-HSA-1839120
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Homo sapiens
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Amplification or activation of FGFR1 has been reported in lung cancer (Weiss, 2001; Marek, 2009; Dutt, 2011), breast cancer (Reis-Filho, 2006; Turner, 2010), oral squamous carcinoma (Freier, 2007), esophageal squamous cell carcinomas (Ishizuka, 2002), ovarian cancer (Gorringe, 2007), bladder cancer (Simon, 2001), prostate cancer (Edwards, 2003; Acevedo, 2007) and rhabodomyosarcoma (Missiaglia, 2009). Unlike the case for FGFR2 amplifications, FGFR1 amplifications are not associated with additional point mutations and affect signaling without altering the intrinsic kinase activity of the receptor. Overexpressed FGFR1 appears to signal at a basal level in a ligand-independent fashion, but is also able to be stimulated by exogenous ligand. Downstream activation may be the result of aberrant paracrine or autocrine stimulation (reviewed in Turner and Gross, 2010; Greulich and Pollock, 2011). FGFR1 amplification has not been conclusively demonstrated to be the causative oncogenic agent in all of the cancer types mentioned above, and other genes in the 8p11 region may also be candidates in some cases (Bass, 2009; Bernard-Pierrot, 2008; Ray, 2004).

Literature References
PubMed ID Title Journal Year
14729606 Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines

Kleer, CG, Albertson, D, Washburn, JG, Ethier, SP, Yang, ZQ, Ray, ME, Macoska, JA

Cancer Res 2004
21160078 Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer

Sietsma, H, Smit, E, Solomon, B, Sollberg, S, Soltermann, A, Sos, ML, Stoelben, E, Thomas, RK, Sänger, J, Timens, W, Thunnissen, E, Wagener, P, Cappuzzo, F, Buettner, R, Brustugun, OT, Brambilla, E, Brambilla, C, Baumann, M, Beroukhim, R, Baessmann, I, Balke-Want, H, Ansén, S, Altmüller, J, Zander, T, Wright, G, Leenders, F, Koker, M, Heynck, S, Klebl, B, Heukamp, LC, Heuckmann, JM, Hallek, M, Heideman, D, Groen, H, Fischer, F, Gabler, F, Ernestus, K, Engel-Riedel, W, Damiani, S, Conron, M, Dabow, I, Clement, J, Seidel, D, Schöttle, J, Russell, P, Rauh, D, Petersen, I, Querings, S, Perner, S, Nürnberg, P, Peifer, M, Moch, H, Menon, R, Ludwig, C, Maier, S, Ligorio, C, Lorimier, P, Wolf, J, Pao, W, Weiss, J, Wainer, Z, Ullrich, RT

Sci Transl Med 2010
19801978 SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Jr, UR, Stairs, DB, Kim, SY, Minna, JD, Rao, S, Komisarof, J, Tamayo, P, Lafargue, CJ, Gat-Viks, I, Regev, A, Bass, AJ, Beer, DG, Gazdar, AF, Tsao, MS, Marie, SK, Giordano, TJ, Lin, L, Ma, C, Rozenblatt-Rosen, O, Ramos, AH, Brose, MS, Verhaak, RG, Rustgi, AK, Wong, KK, Rubin, MA, Hahn, WC, Wagner, P, Meyerson, M, Cecconello, I, Woo, MS, Chirieac, LR, Wardwell, L, Mermel, CH, Scheble, V, Watanabe, H, Dahl, O, Weir, BA, Wilbertz, T, Beroukhim, R, Perner, S, Nakagawa, H, Dziunycz, P, Shivdasani, RA, Getz, G, Dutt, A, Yu, S, O'Kelly, M, Zhu, CQ

Nat Genet 2009
17699850 High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications

Sridhar, A, Campbell, IG, Choong, DY, Qiu, W, Jacobs, S, Gorringe, KL, Thompson, ER

Clin Cancer Res 2007
18757432 Characterization of the recurrent 8p11-12 amplicon identifies PPAPDC1B, a phosphatase protein, as a new therapeutic target in breast cancer

Delattre, O, Pierron, G, Reyal, F, Stransky, N, Bernard-Pierrot, I, Radvanyi, F, Vallot, C, Gruel, N, Raynal, V, Vincent-Salomon, A

Cancer Res 2008
17121884 FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas

Sarrio, D, Hardisson, D, Savage, K, Weber, B, Schmitt, FC, Ashworth, A, Lambros, MB, Reis-Filho, JS, Dexter, T, Iravani, M, Turner, NC, Jones, C, Fenwick, K, Grigoriadis, A, Lakhani, SR, Palacios, J, Simpson, PT, Mackay, A

Clin Cancer Res 2006
11389083 High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer

Jäger, P, Hardmeier, T, Ackermann, D, Wagner, U, Flury, R, Maurer, R, Sauter, G, Knönagel, H, Alund, G, Anabitarte, M, Gasser, T, Hering, F, Moch, H, Schmid, U, Wilber, K, Mihatsch, MJ, Schraml, P, Schönenberger, A, Richter, J, Simon, R, Rist, M, Fehr, JL, Bruderer, J, Fijan, A

Cancer Res 2001
20179196 FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer

Marchio, C, Ashworth, A, Reis-Filho, JS, Lambros, M, Iorns, E, Gillett, C, Geyer, F, Natrajan, R, Sharpe, R, Lopez-Garcia, MA, Turner, N, Tutt, A, Grigoriadis, A, Mackay, A, Pearson, A

Cancer Res 2010
14614009 Gene amplifications associated with the development of hormone-resistant prostate cancer

Witton, CJ, Edwards, J, Bartlett, JM, Krishna, NS

Clin Cancer Res 2003
18068632 Inducible FGFR-1 activation leads to irreversible prostate adenocarcinoma and an epithelial-to-mesenchymal transition

Spencer, DM, Peterson, LE, Wang, F, Acevedo, VD, Li, R, Freeman, KW, Ittmann, M, Ayala, GE, Gangula, RD, Zhang, Y

Cancer Cell 2007
18849352 Fibroblast growth factor (FGF) and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells

Marek, L, Heasley, LE, Helfrich, BA, Coldren, CD, Fritzsche, A, Ware, KE, Hercule, P, McDermott, LA, Helton, WR, Merrick, DT, Nemenoff, RA, Bunn PA, Jr, Smith, JE

Mol Pharmacol 2009
21367659 Targeting mutant fibroblast growth factor receptors in cancer

Pollock, PM, Greulich, H

Trends Mol Med 2011
16807070 Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC)

Hofele, C, Flechtenmacher, C, Schwaenen, C, Mühling, J, Lichter, P, Sticht, C, Radlwimmer, B, Freier, K, Joos, S

Oral Oncol 2007
20094046 Fibroblast growth factor signalling: from development to cancer

Grose, RP, Turner, N

Nat Rev Cancer 2010
21666749 Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Mermel, C, Hammerman, PS, Greulich, H, Gray, NS, Ramos, AH, Cho, J, Chande, A, Dutt, A, Tanaka, KE, Stransky, N, Meyerson, M, Sharifnia, T

PLoS One 2011
12147242 Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH

Tokunaga, A, Sakamoto, H, Matsukura, N, Sasaki, H, Tajiri, T, Ishizuka, T, Tanabe, C, Yoshida, T, Terada, M, Aoyagi, K, Maekawa, M

Biochem Biophys Res Commun 2002
19235922 Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: an approach to identify candidate genes involved in tumor development

Missiaglia, E, Pritchard-Jones, K, Schaaf, G, Selfe, J, Summersgill, B, Versteeg, R, Williamson, D, Hamdi, M, Fang, C, Kool, M, Koster, J, Messahel, B, Shipley, J

Genes Chromosomes Cancer 2009
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Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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