EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients
EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients
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DOI：
10.1007/s11095-005-7094-2
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发表时间：
2005-10-01
影响因子：
3.7
通讯作者：
Okumura, K
中科院分区：
文献类型：
--
作者：
Sakaeda, T;Okamura, N;Okumura, K
目的.最近报道，表皮生长因子受体（EGFR）外显子18、19和21的杂合子体细胞突变与非小细胞肺癌患者对吉非替尼的反应相关。这种突变在日本人中比在欧洲人中更常见。在这项工作中，突变的频率进行了研究，从日本受试者获得的肾细胞癌（RCC）样本，以检查吉非替尼作为治疗剂的RCC的潜力。19例提供书面知情同意书的RCC患者入组本研究。采用实时荧光定量逆转录-聚合酶链反应（RT-PCR）方法检测肾癌组织及癌旁肾组织中EGFR mRNA的表达水平。提取肾癌组织基因组DNA，直接测序法检测体细胞突变。肾癌组织中mRNA的表达是癌旁组织的19倍，但两者均未检测到突变。尽管EGFR在肿瘤进展中起着关键作用，但本研究的结果并不支持对日本患者进行基因分型的肾细胞癌吉非替尼进一步临床试验的有效性。
Purpose. 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.Methods. 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.Results. 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.Conclusion. 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.