title: Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target.
abstract: Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. With the aim of establishing personalized medicine for treatment of solid tumors, we focused on MET amplification in gastric cancer patients, given the extreme sensitivity to c-Met inhibitor in MET amplified gastric cancer cell lines. We tested MET amplification and activation of c-Met in various gastric cancer cell lines and tissue samples from 482 gastric cancer patients who underwent curative surgery. Gastric cancer cell lines with MET amplification by quantitative real-time PCR (qPCR) and FISH predicted sensitivity to PHA-665,752, a selective c-Met kinase inhibitor. Of the 472 patients who had DNA sample available for qPCR analysis, 100 patients (21.2%) had a MET copy number greater than 4.0 copies and demonstrated poorer survival following curative surgery with statistical significance (5-year OS; 50.0 vs. 59.1%; MET amplification (+) vs. MET amplification (-); P = 0.0134). These results suggest that the increased MET copy number measured by qPCR plays an important role in determining prognosis in gastric cancer patients. However, the predictive role of MET amplification for treatment response should be further explored in upcoming clinical trials.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Seo
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Jun
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Min Gew
authors.initials: MG
authors.lastname: Choi
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Bae
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Sohn
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Noh
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
authors.forename: Hey-Lim
authors.initials: HL
authors.lastname: Jang
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met