Abstract 4657: MET amplification as a potential therapeutic target in gastric cancer.

<jats:title>Abstract</jats:title> <jats:p>Purpose</jats:p> <jats:p>Our aim was to investigate both the prevalence of MET amplification in gastric cancer as well as the potential of this genetic alteration to serve as a therapeutic target in gastric cancer.</jats:p> <jats:p>Experimental Design</jats:p> <jats:p>MET amplification was assessed by initial screening with a PCR-based copy number assay followed by confirmatory FISH analysis in formalin-fixed, paraffin-embedded specimens of gastric cancer obtained at surgery. The effects of MET tyrosine kinase inhibitors (MET-TKIs) in gastric cancer cells with or without MET amplification were also examined.</jats:p> <jats:p>Results</jats:p> <jats:p>The median MET copy number in 266 cases of gastric cancer was 1.7, with a range of 0.41 to 21.3. We performed FISH analysis for the 15 cases with the highest MET copy numbers. MET amplification was confirmed in the four assessable cases with a MET copy number of at least 4, whereas MET amplification was not detected in those with a gene copy number of &lt;4. The prevalence of MET amplification was thus 1.5% (4 out of 266 cases). Inhibition of MET by MET-TKIs resulted in the induction of apoptosis accompanied by attenuation of downstream MET signaling in gastric cancer cell lines with MET amplification but not in those without this genetic change.</jats:p> <jats:p>Conclusion</jats:p> <jats:p>MET amplification identifies a small but clinically important subgroup of gastric cancer patients who are likely to respond to MET-TKIs. Furthermore, screening with a PCR-based copy number assay is an efficient way to reduce the number of patients requiring confirmation of MET amplification by FISH analysis.</jats:p> <jats:p>Citation Format: Hisato Kawakami, Isamu Okamoto, Tokuzo Arao, Wataru Okamoto, Kazuko Matsumoto, Hirokazu Taniguchi, Kiyoko Kuwata, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa, Yasuhide Yamada. MET amplification as a potential therapeutic target in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4657. doi:10.1158/1538-7445.AM2013-4657</jats:p>