Evaluation of Kras Gene Mutation and Copy Number Gain in Non-small Cell Lung Cancer
Evaluation of Kras Gene Mutation and Copy Number Gain in Non-small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e31820594f0
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发表时间：
2011-01-01
影响因子：
20.4
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sasaki, Hidefumi;Hikosaka, Yu;Fujii, Yoshitaka
最近对肺癌基因组特征的研究表明，Kras基因经常被扩增，并与Kras激活突变相关，Kras激活突变发生在约5%至10%的日本肺癌中。方法：对172例日本非小细胞肺癌（NSCLC）患者的Kras基因突变、Kras拷贝数及其与患者生存的关系进行分析。我们还研究了利用荧光原位杂交在40个临床标本中提供Kras扩增的直接证据。结果：172例NSCLC患者中，Kras拷贝数增高19例（11.0%）。Kras基因拷贝数增加与Kras突变相关。然而，Kras基因拷贝数增加与性别、病理亚型、分期和吸烟状况无关。在这172例患者中，Kras拷贝数的增加与总生存率无关；然而，Kras拷贝数增加和Kras突变的患者与Kras野生型和Kras未增加的患者相比，预后明显差。从荧光原位杂交分析来看，Kras多体或扩增患者与Kras二体患者相比，预后明显差。结论：Kras突变加上拷贝数增加是NSCLC患者临床预后不良的预测因子。
Introduction: Recent studies for the characterization of the lung cancer genome have suggested that Kras gene was frequently amplified and correlated with activating mutations of Kras, which occur in approximately 5 to 10% of Japanese lung cancers.Methods: We analyzed Kras mutation and Kras copy number in 172 Japanese non-small cell lung cancer (NSCLC) cases and their relation to the survival of patients. We also studied using fluorescence in situ hybridization to provide direct evidence of Kras amplification in 40 clinical specimens.Results: In 172 NSCLC cases, increased Kras copy number existed in 19 (11.0%) cases. Increased Kras gene copy number was correlated with Kras mutation. Nevertheless, Kras gene copy number gain was not correlated with gender, pathological subtypes, stages, and smoking status. Increased Kras copy number was not associated with overall survival in these 172 cases; however, patients with increased Kras copy number and Kras mutant had significantly worse prognosis, when compared with patients with Kras wild type and Kras not increased. From the fluorescence in situ hybridization analysis, Kras polysomy or amplified patients showed significantly worse prognosis, when compared with Kras disomy patients.Conclusion: Kras mutation plus increased copy number was a predictor of poor clinical outcome in patients with NSCLC.