11月30日，PLoS ONE在线发表了中科院上海生科院生化与细胞所季红斌研究组与复旦大学肿瘤医院合作的研究成果 ,该工作在更大样本的基础上进一步建立并完善了非吸烟肺腺癌人群中关键的致癌基因突变谱。
季红斌课题组长期致力于肺癌基因组学的研究。以往在52例肺癌样本中的研究结果表明非吸烟肺腺癌患者来源的肿瘤样本具有特殊的致癌基因突变谱：约90%患者的肿瘤样本中具有EGFR, KRAS, HER2及EML4-ALK四种基因突变中的一种。由于目前临床上已经有一些小分子药物可以有效地抑制突变的EGFR、HER2和ALK的活性，因此绝大多数非吸烟的肺腺癌患者有可能从这些药物的治疗中获益的。
最近季红斌研究组在前期工作基础上进行了更大规模和更为深入的分析：在202例非吸烟肺腺癌患者来源的肿瘤样本中，对EGFR, KRAS, HER2, ALK突变以及最近发现的ROS1基因融合进行了检测以及临床相关性分析。研究结果表明，大约89%患者的肿瘤样本中具有而且只具有以上五种突变中的一种。这一工作不但证实了该课题组以往的研究结果，而且发现EGFR突变的患者与非EGFR突变的患者相比年龄偏大(58.3 Vs 54.3, P = 0.016)，而存在未知基因突变的患者与具有已知突变的患者相比年龄偏小 (52.3 Vs 57.9, P = 0.013)。该研究将为临床的个体化分子靶向治疗提供理论依据。(生物谷Bioon.com)
doi:10.1371/journal.pone.0028204
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Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers
Chenguang Li, Rong Fang, Yihua Sun, Xiangkun Han, Fei Li, Bin Gao, A. John Iafrate, Xin-Yuan Liu, William Pao, Haiquan Chen, Hongbin Ji
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.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.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.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.
