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MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients

Cappuzzo, F. and Jänne, P. A. and Skokan, M. and Finocchiaro, G. and Rossi, E. and Ligorio, C. and Zucali, P. A. and Terracciano, L. and Toschi, L. and Roncalli, M. and Destro, A. and Incarbone, M. and Alloisio, M. and Santoro, A. and Varella-Garcia, M.. (2009) MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients. Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 20. pp. 298-304.

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Official URL: http://edoc.unibas.ch/dok/A6002995

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Terracciano, Luigi M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0923-7534
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:13

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