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FGFR2 gene amplification and clinicopathological features in gastric cancer
K Matsumoto1, T Arao, T Hamaguchi
1Department of Genome Biology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan.
Background:
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.
Methods:
Drug sensitivity to a fibroblast growth factor receptor (FGFR) inhibitor was evaluated in vitro. 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 and fluorescence in situ hybridisation (FISH).
Results:
FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members (FGFR1, 3 and 4) was detected. A FISH analysis was performed on 7 cases among 11 FGFR2-amplified cases and showed that 6 of these 7 cases were highly amplified, while the remaining 1 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.
Conclusion:
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.
Insights
Fibroblast growth factor receptor 2 (FGFR2) amplification occurs in 4.1% of gastric cancers. This finding supports developing FGFR-targeted therapies for patients with FGFR2-amplified gastric cancer.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- The frequency and clinical significance of FGFR2 amplification in gastric cancer are not well understood.
- High-throughput screening data for FGFR2 amplification in large gastric cancer cohorts are limited.
Purpose of the Study:
- To determine the frequency of FGFR2 amplification in gastric cancer.
- To investigate the clinicopathological features associated with FGFR2 amplification.
- To evaluate the efficacy of FGFR inhibitors in gastric cancer models with FGFR2 amplification.
Main Methods:
- Real-time PCR-based copy number assay and fluorescence in situ hybridization (FISH) were used to detect FGFR gene amplification in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues.
- Drug sensitivity assays were performed in vitro to assess the response to a fibroblast growth factor receptor (FGFR) inhibitor.
Main Results:
- FGFR2 amplification was detected in 4.1% (11/267) of gastric cancers; no amplification of FGFR1, FGFR3, or FGFR4 was observed.
- FGFR2-amplified gastric cancer cell lines demonstrated hypersensitivity to an FGFR inhibitor.
- FISH analysis confirmed high-level amplification in 6 out of 7 cases with FGFR2 amplification.
- A trend towards shorter overall survival was noted in patients with FGFR2 amplification, though not statistically significant.
Conclusions:
- FGFR2 amplification is present in a subset of gastric cancers and can be reliably detected using a PCR-based assay on FFPE samples.
- The study provides a strong rationale for developing FGFR-targeted therapies for gastric cancers harboring FGFR2 amplification.
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