Wang Zhen, Wu Yi Long, Zhang Guo Chun, Zhou Qing, Xu Chong Rui, Guo Ai Lin
Guangdong Provincial People's Hospital, Cancer Center, Guangdong Provincial Lung Cancer Research Institute, Guangzhou, China.
Onkologie. 2008 Apr;31(4):174-8. doi: 10.1159/000116736. Epub 2008 Mar 20.
For gefitinib treatment for non-small cell lung cancer (NSCLC), KRAS mutations reportedly behave as a resistance marker, and the epidermal growth factor receptor (EGFR) as a responsive marker. It is known that Asians and Caucasians have different responses to gefitinib. We investigated the KRAS and EGFR mutation status in a group of Chinese patients with advanced NSCLC who were treated with gefitinib after a failed chemotherapy.
Genomic DNA extracted from tumor specimens of 24 patients with advanced NSCLC, who failed at least 1 prior platinum-based chemotherapy regimen before gefitinib treatment, was subjected to nested polymerase chain reaction (PCR) to amplify codons 12, 13, 59, and 61 of the KRAS gene and exons 18-21 of the EGFR gene for direct sequencing.
For the 24 patients, no KRAS gene mutation was found. 15 patients (62.5%, 15/24) harbored EGFR mutations which included deletion mutations in exon 19 and missense mutations in exon 21.
KRAS mutation may occur at a very low frequency in Chinese NSCLC patients regardless of pathology, smoking status, or gender. Unlike EGFR, the low incidence of KRAS mutations may undermine its role in predicting the clinical response to EGFR tyrosine kinase inhibitors.
据报道,在吉非替尼治疗非小细胞肺癌(NSCLC)中,KRAS突变表现为耐药标志物,而表皮生长因子受体(EGFR)则为反应性标志物。已知亚洲人和高加索人对吉非替尼的反应不同。我们调查了一组晚期NSCLC中国患者在化疗失败后接受吉非替尼治疗时的KRAS和EGFR突变状态。
从24例晚期NSCLC患者的肿瘤标本中提取基因组DNA,这些患者在接受吉非替尼治疗前至少有1次铂类化疗方案失败,对其进行巢式聚合酶链反应(PCR)以扩增KRAS基因的第12、13、59和61密码子以及EGFR基因的第18 - 21外显子,用于直接测序。
24例患者中未发现KRAS基因突变。15例患者(62.5%,15/24)存在EGFR突变,包括第19外显子缺失突变和第21外显子错义突变。
无论病理类型、吸烟状况或性别如何,中国NSCLC患者中KRAS突变的发生率可能非常低。与EGFR不同,KRAS突变的低发生率可能会削弱其在预测对EGFR酪氨酸激酶抑制剂临床反应中的作用。