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MET Gene Copy Number in Non-small Cell Lung Cancer: Molecular Analysis in a Targeted Tyrosine Kinase Inhibitor Naive Cohort.
Beau-Faller, Michele MD, PhD *+; Ruppert, Anne-Marie MD ++; Voegeli, Anne-Claire PD *; Neuville, Agnes MD [S]; Meyer, Nicolas MD, PhD [//]; Guerin, Eric PD, PhD *; Legrain, Michele PhD *; Mennecier, Bertrand MD ++; Wihlm, Jean-Marie MD [P]; Massard, Gilbert MD [P]; Quoix, Elisabeth MD *; Oudet, Pierre MD *+; Gaub, Marie P. PhD *
[Article] Journal of Thoracic Oncology. 3(4):331-339, April 2008.

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Introduction: Recent clinical success of epidermal growth factor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) have raised hopes that targeting other deregulated growth factor signaling, such as the hepatocyte growth factor/MET pathway, will lead to new therapeutic options for NSCLC. Furthermore, NSCLC present secondary EGFR-TKIs resistance related to exons 20 and 19 EGFR mutations or more recently to MET amplification. The aim of this study was to determine MET copy number related to EGFR copy number and K-Ras mutations in a targeted TKI naive NSCLC cohort.

Methods: We investigated 106 frozen tumors from surgically resected NSCLC patients. Genes copy number of MET and EGFR were assessed by quantitative relative real-time polymerase chain reaction and K-Ras mutations by sequencing.

Results: MET is amplified in 22 cases (21%) and deleted in nine cases (8.5%). EGFR is amplified in 31 cases (29%). K-Ras is mutated in 11 cases (10.5%). As observed for EGFR amplification, MET amplification is never associated with K-Ras mutation. MET amplification could be associated with EGFR amplification. MET amplification is not related to clinical and pathologic features. MET amplification and EGFR amplification showed a trend toward poor prognosis in adenocarcinomas.

Conclusion: In EGFR-TKIs naive NSCLC patients, MET amplification is a frequent event, which could be associated with EGFR amplification, but not with K-Ras mutation. MET amplification may identify a subset of NSCLC for new targeted therapy. It will also be important to evaluate MET copy number to properly interpret future clinical trials.