MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer.
MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer.
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MET 外显子 14 跳跃定义了非小细胞肺癌的独特分子类别
DOI：
10.18632/oncotarget.9541
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发表时间：
2016-07-05
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Zheng D;Wang R;Ye T;Yu S;Hu H;Shen X;Li Y;Ji H;Sun Y;Chen H
目的在肺癌中发现了MET第14号外显子的重复剪接，这是一个有前途的治疗靶点。由于我们对MET突变型肿瘤的自然史了解有限，目前的研究旨在确定非小细胞肺癌（NSCLC）的临床和病理特征。结果23例（1.3%）患者MET外显子14跳读阳性。MET外显子14跳读患者具有独特的特征：女性、不吸烟、病理分期较早和年龄较大。MET外显子14跳读表明肺癌中的其他驱动因素是早期事件，而MET拷贝数增加更可能是肺癌中的晚期事件。携带MET外显子14跳跃的患者的总生存期（OS）长于KRAS突变患者。几乎五分之四的MET外显子14跳读的肺肿瘤具有EGFR和/或HER 2基因拷贝数增加。EGFR抑制剂在治疗携带MET外显子14跳跃的患者中显示出中度抗肿瘤活性。患者和方法从2007年10月至2013年6月，我们筛选了1770例NSCLC患者，并将MET状态与临床病理特征和EGFR、KRAS、BRAF、HER 2和ALK突变相关。实时荧光定量PCR检测MET基因拷贝数增加。还进行免疫组织化学（IHC）以筛选MET外显子14跳读。分析患者的临床病理特征和生存情况。结论1.3%（23/1770）的中国非小细胞肺癌患者存在MET第14号外显子跳读。MET外显子14跳读定义了一个新的具有可识别临床特征的NSCLC分子亚群。治疗性EGFR抑制剂可能是MET突变型NSCLC患者的替代治疗。
Purpose Recurrent MET exon 14 splicing has been revealed in lung cancers and is a promising therapeutic target. Because we have limited knowledge about the natural history of MET mutant tumors, the current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC). Results Twenty-three patients (1.3%) were positive for MET exon 14 skipping. Patients with MET exon 14 skipping displayed unique characteristics: female, non-smokers, earlier pathology stage and older age. MET exon 14 skipping indicated an early event as other drivers in lung cancer, while MET copy number gain was more likely a late event in lung cancer. Overall survival (OS) of patients harboring MET exon 14 skipping was longer than patients with KRAS mutation. Almost four-fifths of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. EGFR inhibitor showed moderate antitumor activity in treatment of a patient harboring MET exon 14 skipping. Patients and Methods From October 2007 to June 2013, we screened 1770 patients with NSCLC and correlated MET status with clinical pathologic characteristics and mutations in EGFR, KRAS, BRAF, HER2, and ALK. Quantitative Real-Time PCR was used to detect MET gene copy number gain. Immunohistochemistry (IHC) was also performed to screen MET exon 14 skipping. Clinicopathological characteristics and survival information were analyzed. Conclusions MET exon 14 skipping was detected in 1.3% (23/1770) of the Chinese patients with NSCLC. MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. The therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
5.3
作者：
Li, Hang;Pan, Yunjian;Chen, Haiquan
通讯作者：
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影响因子：
9.6
作者：
Pan, Yunjian;Wang, Rui;Chen, Haiquan
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影响因子：
3.6
作者：
Jenkins RW;Oxnard GR;Elkin S;Sullivan EK;Carter JL;Barbie DA
通讯作者：
Barbie DA
DOI：
10.1073/pnas.0710370104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Bean, James;Brennan, Cameron;Pao, William
通讯作者：
Pao, William