EGFR mRNA is Upregulated, but Somatic Mutations of the Gene are Hardly Found in Renal Cell Carcinoma in Japanese Patients
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- Sakaeda, T., Okamura, N., Gotoh, A. et al. Pharm Res (2005) 22: 1757. doi:10.1007/s11095-005-7094-2
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Heterozygous somatic mutations of epidermal growth factor receptor (EGFR) in exons 18, 19, and 21 were recently reported to be associated with response to gefitinib in patients having nonsmall cell lung cancer. Such mutations are more frequently found among Japanese than Europeans. In this work, the frequency of mutations was investigated in renal cell carcinoma (RCC) samples obtained from Japanese subjects to examine the potential of gefitinib as a therapeutic agent for RCC.
Nineteen patients with RCC, who gave written informed consent, were enrolled in this study. mRNA expression levels of EGFR were measured in RCC and its adjacent noncancerous renal tissue via the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Somatic mutations were determined using genomic DNA extracted from RCC by direct sequencing method.
mRNA expression was confirmed to be about 19 times higher in RCC than in adjacent noncancerous renal tissues, but no such mutations were detected in both.
Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.
Key WordsEGF receptorrenal cell carcinomasomatic mutation
chronic myelogenous leukemia
epidermal growth factor receptor
human epidermal growth factor receptor
Iressa dose evaluation in advanced lung cancer
Iressa NSCLC trial assessing combination treatment
nonsmall cell lung cancer
polymerase chain reaction
renal cell carcinoma