Frequency of EGFR and KRAS Mutations in Lung Adenocarcinomas in African Americans
Frequency of EGFR and KRAS Mutations in Lung Adenocarcinomas in African Americans
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DOI：
10.1097/jto.0b013e3181fb4fe2
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发表时间：
2011-01-01
影响因子：
20.4
通讯作者：
Kris, Mark G.
中科院分区：
文献类型：
--
作者：
Reinersman, J. Matthew;Johnson, Melissa L.;Kris, Mark G.
简介：表皮生长因子受体（EGFR）基因突变的检测，可预测EGFR酪氨酸激酶抑制剂治疗的敏感性，代表了肺腺癌治疗的重大进展。KRAS突变赋予EGFR-酪氨酸激酶抑制剂抗性。这些突变的患病率在非洲裔美国人patients.Methods：我们收集了福尔马林固定，石蜡包埋的材料从切除的肺腺癌从非洲裔美国人的患者在三个机构的DNA提取。将来自非洲裔美国患者的肿瘤标本中EGFR 19号外显子缺失、21号外显子L 858 R置换和KRAS突变的频率与白色患者的数据（n = 476）进行比较。（19%，95%置信区间[CI]：13-27%），而在21例患者中发现KRAS突变（17%，95% CI：12-25%）。非裔美国人和白色患者的EGFR突变频率无显著差异，分别为19%和13%（61/476，95% CI：10-16%; p = 0.11）。KRAS突变在白人中更有可能，26%（125/476，95%CI：23-30%; p = 0.04）.结论：这是迄今为止最大的研究，研究了非裔美国人肺腺癌的突变频率。虽然KRAS突变的可能性较小，但与白人相比，非裔美国人患者中EGFR突变的频率没有差异。这些结果表明，所有晚期肺腺癌患者在开始治疗前应进行突变分析。
Introduction: The detection of mutations in the epidermal growth factor receptor (EGFR) gene, which predict sensitivity to treatment with EGFR tyrosine kinase inhibitors, represents a major advance in the treatment of lung adenocarcinoma. KRAS mutations confer resistance to EGFR-tyrosine kinase inhibitors. The prevalence of these mutations in African American patients has not been thoroughly investigated.Methods: We collected formalin-fixed, paraffin-embedded material from resected lung adenocarcinomas from African American patients at three institutions for DNA extraction. The frequencies of EGFR exon 19 deletions, exon 21 L858R substitutions, and KRAS mutations in tumor specimens from African American patients were compared with data in white patients (n = 476).Results: EGFR mutations were detected in 23 of the 121 specimens from African American patients (19%, 95% confidence interval [CI]: 13-27%), whereas KRAS mutations were found in 21 (17%, 95% CI: 12-25%). There was no significant difference between frequencies of EGFR mutations comparing African American and white patients, 19% versus 13% (61/476, 95% CI: 10-16%; p = 0.11). KRAS mutations were more likely among whites, 26% (125/476, 95% CI: 23-30%; p = 0.04).Conclusions: This is the largest study to date examining the frequency of mutations in lung adenocarcinomas in African Americans. Although KRAS mutations were somewhat less likely, there was no difference between the frequencies of EGFR mutations in African American patients, when compared with whites. These results suggest that all patients with advanced lung adenocarcinomas should undergo mutational analysis before initiation of therapy.