BACKGROUND: MET amplification has been detected in approximately 20% of non-small-cell lung cancer patients (NSCLC) with epidermal growth factor receptor (EGFR) mutations progressing after an initial response to tyrosine kinase inhibitor (TKI) therapy. PATIENTS AND METHODS: We analyzed MET gene copy number using FISH in two related NSCLC cell lines, one sensitive (HCC827) and one resistant (HCC827 GR6) to gefitinib therapy and in two different NSCLC patient populations: 24 never smokers or EGFR FISH-positive patients treated with gefitinib (ONCOBELL cohort) and 182 surgically resected NSCLC not exposed to anti-EGFR agents. RESULTS: HCC827 GR6-resistant cell line displayed MET amplification, with a mean MET copy number >12, while sensitive HCC827 cell line had a mean MET copy number of 4. In the ONCOBELL cohort, no patient had gene amplification and MET gene copy number was not associated with outcome to gefitinib therapy. Among the surgically resected patients, MET was amplified in 12 cases (7.3%) and only four (2.4%) had a higher MET copy number than the resistant HCC827 GR6 cell line. CONCLUSIONS: MET gene amplification is a rare event in patients with advanced NSCLC. The development of anti-MET therapeutic strategies should be focused on patients with acquired EGFR-TKI resistance.
BACKGROUND: MET amplification has been detected in approximately 20% of non-small-cell lung cancerpatients (NSCLC) with epidermal growth factor receptor (EGFR) mutations progressing after an initial response to tyrosine kinase inhibitor (TKI) therapy. PATIENTS AND METHODS: We analyzed MET gene copy number using FISH in two related NSCLC cell lines, one sensitive (HCC827) and one resistant (HCC827 GR6) to gefitinib therapy and in two different NSCLCpatient populations: 24 never smokers or EGFR FISH-positive patients treated with gefitinib (ONCOBELL cohort) and 182 surgically resected NSCLC not exposed to anti-EGFR agents. RESULTS: HCC827 GR6-resistant cell line displayed MET amplification, with a mean MET copy number >12, while sensitive HCC827 cell line had a mean MET copy number of 4. In the ONCOBELL cohort, no patient had gene amplification and MET gene copy number was not associated with outcome to gefitinib therapy. Among the surgically resected patients, MET was amplified in 12 cases (7.3%) and only four (2.4%) had a higher MET copy number than the resistant HCC827 GR6 cell line. CONCLUSIONS: MET gene amplification is a rare event in patients with advanced NSCLC. The development of anti-MET therapeutic strategies should be focused on patients with acquired EGFR-TKI resistance.
Authors: J Guillermo Paez; Pasi A Jänne; Jeffrey C Lee; Sean Tracy; Heidi Greulich; Stacey Gabriel; Paula Herman; Frederic J Kaye; Neal Lindeman; Titus J Boggon; Katsuhiko Naoki; Hidefumi Sasaki; Yoshitaka Fujii; Michael J Eck; William R Sellers; Bruce E Johnson; Matthew Meyerson Journal: Science Date: 2004-04-29 Impact factor: 47.728
Authors: Haiming Luo; Hao Hong; Michael R Slater; Stephen A Graves; Sixiang Shi; Yunan Yang; Robert J Nickles; Frank Fan; Weibo Cai Journal: J Nucl Med Date: 2015-04-03 Impact factor: 10.057
Authors: Christian Rolfo; Francesco Passiglia; Marta Castiglia; Luis E Raez; Paul Germonpre; Ignacio Gil-Bazo; Karen Zwaenepoel; Annemieke De Wilde; Giuseppe Bronte; Antonio Russo; Jan P Van Meerbeeck; Paul Van Schil; Patrick Pauwels Journal: Transl Lung Cancer Res Date: 2014-08
Authors: Tobias Ach; Katharina Zeitler; Stephan Schwarz-Furlan; Katharina Baader; Abbas Agaimy; Christian Rohrmeier; Johannes Zenk; Martin Gosau; Torsten E Reichert; Gero Brockhoff; Tobias Ettl Journal: Virchows Arch Date: 2012-12-15 Impact factor: 4.064