Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status.
Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status.
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基于组织学和吸烟状况鉴定非小细胞肺癌患者亚组中丰富的驱动基因改变。
DOI：
10.1371/journal.pone.0040109
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wu YL
中科院分区：
文献类型：
--
作者：
An SJ;Chen ZH;Su J;Zhang XC;Zhong WZ;Yang JJ;Zhou Q;Yang XN;Huang L;Guan JL;Nie Q;Yan HH;Mok TS;Wu YL
对于仅对特定遗传改变患者有效的靶向治疗，需要适当的患者选择。我们的目标是定义非小细胞肺癌患者中具有候选驱动基因的患者亚组。入选在广东省人民医院接受临床基因检测的原发性肺癌患者。通过测序、高分辨率熔解分析、qPCR或多重PCR和RACE方法检测驱动基因。524例患者入组本研究，并根据组织学和吸烟状况分析亚组之间驱动基因改变的差异。在非吸烟腺癌患者亚组中，EGFR是最常见的改变基因，突变率为49.8%，其次是EML 4-ALK（9.3%）、PTEN（9.1%）、PIK 3CA（5.2%）、c-Met（4.8%）、KRAS（4.5%）、STK 11（2.7%）和BRAF（1.9%）。在吸烟腺癌患者亚组中，三个最常见的改变基因是EGFR（22.0%）、STK 11（19.0%）和KRAS（12.0%）。我们仅在非吸烟者伴鳞状细胞癌（SCC）亚组中发现EGFR（8.0%）、c-Met（2.8%）和PIK 3CA（2.6%）改变。PTEN（16.1%）、STK 11（8.3%）和PIK 3CA（7.2%）是吸烟者SCC中最常见的三个基因。DDR2和FGFR 2仅在吸烟的SCC患者中出现（分别为4.4%和2.2%）。在这四个亚组中，EGFR、KRAS和PTEN突变的差异具有统计学意义。基于组织学和吸烟状况的不同亚组中驱动基因改变的独特特征有助于定义未来针对这些基因的临床试验的患者。这项研究还表明，我们可以将驱动基因罕见改变的患者视为患有罕见或孤儿疾病，应该使用特殊的分子靶向治疗进行管理。
Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies.
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