Somatic Mutation Spectrum of Non-Small-Cell Lung Cancer in African Americans A Pooled Analysis
Somatic Mutation Spectrum of Non-Small-Cell Lung Cancer in African Americans A Pooled Analysis
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DOI：
10.1097/jto.0000000000000650
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发表时间：
2015-10-01
影响因子：
20.4
通讯作者：
Carbone, David P.
中科院分区：
文献类型：
--
作者：
Araujo, Luiz H.;Lammers, Philip E.;Carbone, David P.
简介：非小细胞肺癌（NSCLC）的突变谱已成为对患者进行定制治疗的重要工具，根据起源人群存在明显差异。非裔美国人（AAs）的肺癌发病率和死亡率高于白种人，但有关体细胞驱动突变频率的结果却存在差异。我们假设NSCLC在该组中具有独特的突变谱。方法：我们收集了来自田纳西州、密歇根州和俄亥俄州五个地区的非小细胞肺癌样本。通过SNaPshot或下一代测序评估基因突变，并通过荧光原位杂交评估ALK易位。结果：共纳入260例患者，主要为男性（62.3%）和吸烟者（86.6%）。81例（31.2%）为鳞状细胞癌。最常见的突变基因是KRAS（15.4%）、表皮生长因子受体（EGFR, 5.0%）、PIK3CA（0.8%）、BRAF、NRAS、ERBB2和AKT1（各0.4%）。在2例（1.7%）非鳞状肿瘤中检测到ALK易位，总共61例（23.5%）有驱动的致癌改变。179例非鳞状标本中，54例（30.2%）出现驱动因子改变。总的来说，驱动基因改变的频率低于在白种人中报道的频率，而在EGFR或KRAS突变中没有发现差异。EGFR突变患者的总生存期更长。结论：我们证明来自AAs的非小细胞肺癌与来自白种人的非小细胞肺癌具有不同的体细胞驱动突变模式。这一组中大多数驱动因素的改变尚未被描述，这将需要更全面的小组和非规范改变的评估。
Introduction: The mutational profile of non-small-cell lung cancer (NSCLC) has become an important tool in tailoring therapy to patients, with clear differences according to the population of origin. African Americans (AAs) have higher lung cancer incidence and mortality than Caucasians, yet discrepant results have been reported regarding the frequency of somatic driver mutations. We hypothesized that NSCLC has a distinct mutational profile in this group.Methods: We collected NSCLC samples resected from self-reported AAs in five sites from Tennessee, Michigan, and Ohio. Gene mutations were assessed by either SNaPshot or next generation sequencing, and ALK translocations were evaluated by fluorescence in situ hybridization.Results: Two hundred sixty patients were included, mostly males (62.3%) and smokers (86.6%). Eighty-one samples (31.2%) were squamous cell carcinomas. The most frequently mutated genes were KRAS (15.4%), epidermal growth factor receptor (EGFR, 5.0%), PIK3CA (0.8%), BRAF, NRAS, ERBB2, and AKT1 (0.4% each). ALK translocations were detected in two nonsquamous tumors (1.7%), totaling 61 cases (23.5%) with driver oncogenic alterations. Among 179 nonsquamous samples, 54 (30.2%) presented a driver alteration. The frequency of driver alterations altogether was lower than that reported in Caucasians, whereas no difference was detected in either EGFR or KRAS mutations. Overall survival was longer among patients with EGFR mutations.Conclusions: We demonstrated that NSCLC from AAs has a different pattern of somatic driver mutations than from Caucasians. The majority of driver alterations in this group are yet to be described, which will require more comprehensive panels and assessment of noncanonical alterations.