Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi branch, Taiwan.
Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi branch, Taiwan.
PLoS One. 2019 Aug 1;14(8):e0220670. doi: 10.1371/journal.pone.0220670. eCollection 2019.
Somatic mutations of MET gene are emerging as important driver mutations for lung cancers. To identify the common clinicopathological features of MET exon 14 skipping mutations and amplification and clarify whether the two MET gene alterations cause protein overexpression were investigated using 196 lung cancer samples of Taiwan through real time-qPCR/sequencing, fluorescence in situ hybridization, and immunohistochemistry. The two MET gene alterations are both present in low frequency, ~1%, in the studied lung cancer population of Taiwan. MET exon 14 skipping mutations were identified from two early-stage patients, who were both relatively advanced in age, and did not carry other driver mutations. One was an adenocarcinoma and the other was a rare carcinosarcoma. Three gene amplifications cases were identified. Neither of the two MET gene alterations would lead to protein overexpression; hence, direct detection in nucleic acid level would be a preferred and straightforward solution for the identification of skipping mutations. The presence of MET exon 14 mutations in minor histological types of lung cancers urge to extend screening scope of this mutation in lung cancer and treatment response evaluation in clinical trials. These would be important next steps for the success of MET target therapy in clinical practice.
MET 基因的体细胞突变正在成为肺癌的重要驱动突变。为了确定 MET 外显子 14 跳跃突变和扩增的常见临床病理特征,并阐明这两种 MET 基因改变是否导致蛋白过表达,本研究通过实时 qPCR/测序、荧光原位杂交和免疫组织化学分析了来自台湾的 196 例肺癌样本。这两种 MET 基因改变在台湾的研究肺癌人群中的频率都较低,约为 1%。MET 外显子 14 跳跃突变从两名早期患者中检出,这两名患者年龄都较大,且不携带其他驱动突变。一名患者为腺癌,另一名患者为罕见的癌肉瘤。鉴定出 3 个基因扩增病例。这两种 MET 基因改变都不会导致蛋白过表达;因此,直接在核酸水平上进行检测将是识别跳跃突变的首选和直接方法。MET 外显子 14 突变在肺癌的次要组织学类型中存在,这促使我们扩大该突变在肺癌筛查中的范围,并在临床试验中评估治疗反应。这些将是 MET 靶向治疗在临床实践中取得成功的重要后续步骤。