Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers.
Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers.
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东亚从不吸烟者肺腺癌的致癌驱动突变谱
DOI：
10.1371/journal.pone.0028204
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ji H
中科院分区：
文献类型：
--
作者：
Li C;Fang R;Sun Y;Han X;Li F;Gao B;Iafrate AJ;Liu XY;Pao W;Chen H;Ji H
研究目的：我们先前发现，90%（47/52; 95%CI，0.79 - 0.96）的东亚从不吸烟者的肺腺癌仅在4个基因中存在已知的致癌突变：EGFR、HER2、ALK和KRAS。在这里，我们试图将这些发现扩展到更多的样本，并确定这些突变阴性的肿瘤中的驱动改变。实验设计我们收集并分析了复旦大学附属肿瘤医院202例从不吸烟的肺腺癌切除标本。由于在前52例检查中突变是相互排斥的，因此我们按照先前描述的逐步方式确定了EGFR、KRAS、HER2、ALK和BRAF的状态。随后通过RT-PCR和直接测序检查这5个基因突变阴性的样品中已知的ROS1融合。结果EGFR突变152例（75.3%），HER2突变12例（6%），ALK融合10例（5%），均以EML 4为5 ′端伴侣，KRAS突变4例（2%），ROS 1融合2例（1%）。未检测到BRAF突变。结论绝大多数（176/202; 87.1%，95%CI：0.82 - 0.91）从不吸烟的肺腺癌携带对TKI敏感的突变激酶。有趣的是，EGFR突变患者往往比无EGFR突变的患者年龄更大（58.3 vs 54.3，P = 0.016），而无任何已知致癌驱动因素的患者往往在更年轻时被诊断（52.3 vs 57.9，P = 0.013）。 总的来说，这些数据表明，大多数从不吸烟的肺腺癌患者可以从特定的酪氨酸激酶抑制剂治疗中获益。
Purpose We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations. Experimental Design We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing. Results 152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5′ partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected. Conclusion The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor.
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