Smoking status and self-reported race affect the frequency of clinically relevant oncogenic alterations in non-small-cell lung cancers at a United States-based academic medical practice.
Smoking status and self-reported race affect the frequency of clinically relevant oncogenic alterations in non-small-cell lung cancers at a United States-based academic medical practice.
复制标题
DOI：
10.1016/j.lungcan.2013.07.013
复制
发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Costa DB
中科院分区：
文献类型：
--
作者：
Yamaguchi N;Vanderlaan PA;Folch E;Boucher DH;Canepa HM;Kent MS;Gangadharan SP;Majid A;Kocher ON;Goldstein MA;Huberman MS;Costa DB
识别非小细胞肺癌（NSCLC）的体细胞基因组畸变是NSCLC患者护理循证实践指南的一部分。我们试图在常规患者-肿瘤样本对中确定这些变化的频率和相关性。回顾性收集并分析了381例患者肿瘤样本的临床病理学数据和肿瘤基因型。在这些患者中，75.9%自我报告为白色人种，13.1%为亚洲人，6.5%为黑人，27.8%为从不吸烟者，54.9%为既往吸烟者，17.3%为当前吸烟者。肿瘤样本中EGFR突变频率为23.9%（86/359），KRAS突变频率为34.2%（71/207），ALK FISH阳性频率为9.1%（23/252），几乎所有这些癌基因的结果相互排斥。在白色、黑人和亚洲患者的肿瘤中，EGFR突变频率分别为18.4%、18.2%和62%; ALK FISH阳性频率分别为7.81%、0%和14.8%; KRAS突变频率分别为41.6%、20%和0%。这些模式改变显着增加包年吸烟史。在白色患者中，EGFR突变和ALK FISH阳性的频率随着包-年队列的增加而降低;而KRAS突变的频率增加。有趣的是，在亚洲患者中，EGFR突变的频率在从不吸烟者和吸烟史小于45包年的队列中相似，仅在45包年以上队列中降低。使用来自我们美国学术医疗实践的常规肺癌组织样本，体细胞EGFR、KRAS和ALK基因异常的频率反映了我们检测人群的种族多样性（亚洲患者中EGFR突变频率较高）和吸烟模式（EGFR突变与ALK重排之间呈负相关）。这些结果可能有助于其他医疗实践欣赏从常规肿瘤基因分型技术引入到他们的日常护理NSCLC的预期结果。
The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates of these changes in routine patient-tumor sample pairs. Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient-tumor samples. Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9%(86/359), KRAS mutations 34.2%(71/207) and ALK FISH positivity 9.1%(23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less then 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC.