Met gene copy number predicts the prognosis for completely resected non-small cell lung cancer

The Met oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF). Uncontrolled activation of Met is oncogenic and has been implicated in the growth, invasion and metastasis in a variety of tumors. Several distinct mechanisms including amplification, translocation or mutation of Met may underlie uncontrolled Met activation. In several solid tumors, amplification and mutation of Met were reported to be associated with tumorigenesis, invasion and metastasis. The present study evaluated the amplification and mutation of Met in a large number of non-small cell lung cancer (NSCLC). Among 213 NSCLC patients, increased Met copy number was identified in 12 patients (5.6%) and associated with a worse prognosis (P = 0.0414). The mutation of Met in 534 NSCLC patients was also evaluated. In these patients there were no previously reported mutations within the juxtamembrane (JM) domain (R988C, T1010I, S1058P and G1085X). However, a somatic exon 14 deleting splice variant in 3 (1.7%) of 178 NSCLC samples was identified for which sequencing was performed. Met amplification and mutation were rare in Japanese NSCLC. However, the results support a critical role of Met gene dose in NSCLC, suggesting that Met may be a specific molecular therapeutic target in selected NSCLC patients with increased Met copy number. (Cancer Sci 2008; 99: 2280-2285).