Abstract 5: Frequency of FGFR2 gene amplification in gastric cancer

Abstract

Abstract Background: FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. However, the frequency of FGFR2 amplification, its clinicopathological features, and the results of high throughput screening assays in a large cohort of gastric clinical samples remain largely unclear. Patients and methods: The expression levels of FGFR2 mRNA and proteins, the drug sensitivity to an FGFR inhibitor, and the genomic copy numbers of FGFR1-4 were evaluated in gastric cancer cell lines. The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay. For confirming the results, fluorescence in situ hybridization (FISH) was conducted. Results: All of the four gastric cancer cell lines with FGFR2 amplification were sensitive to an FGFR inhibitor. The above copy number assay and FISH analysis revealed that 4.1% (11/267) of the gastric cancers harbored FGFR2 amplification (intestinal type, n=2; diffuse type, n=8 and unclassified type, n=1). No amplification of the three other family members was detected. A FISH analysis showed that six of these seven cases were highly amplified, while the remaining one had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period. Conclusions: FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5. doi:1538-7445.AM2012-5