title: FGFR2 gene amplification and clinicopathological features in gastric cancer.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Arao
authors.forename: T
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: I
authors.initials: I
authors.lastname: Oda
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
authors.forename: F
authors.initials: F
authors.lastname: Koizumi
authors.forename: K
authors.initials: K
authors.lastname: Yanagihara
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D011743:Pyrimidines / Q000494:pharmacology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: C115711:PD 173074; D011743:Pyrimidines; D051497:Receptor, Fibroblast Growth Factor, Type 2