在MET放大ALK阳性肺癌中的分子异质性和共同改变的基因:对MET向疗法的影响
Ibiayi Dagogo-Jack1, Lesli A Kiedrowski2, Jochen K Lennerz3
1Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, USA; Harvard Medical School, Center for Integrated Diagnostics, Massachusetts General Hospital, USA.
Lung cancer (Amsterdam, Netherlands)
|October 9, 2023
概括
在ALK重组的肺癌中,MET放大通常在组织中显示出高水平的异质放大,很少在血中出现. 这种分子形状经常与与侵略性瘤生物学相关的变化同时发生.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 增强MET是一种已知的抵抗机制,可以抑制形淋巴瘤激酶 (ALK) 抑制剂.
- 对联合ALK和MET向治疗的反应的持续时间在MET放大ALK重组 (ALK+) 肺癌中有所不同,这表明瘤异质性.
- 用MET放大进行ALK重组的非小细胞肺癌 (NSCLC) 的分子格局仍然不太清楚.
研究的目的:
- 为了研究ALK重组NSCLC的分子特征,同时进行MET放大.
- 量化MET拷贝数,并描述这些瘤中共同改变的基因的全球分子景观.
- 为了比较MET放大ALK+NSCLC在组织和血中的分子概况.
主要方法:
- 从组织和血数据库收集了50多个样本,其中包括ALK重组和MET放大.
- 使用光现场杂交 (FISH) 来量化MET复制号.
- 采用下一代测序 (NGS) 来分析全球分子格局并识别共同改变的基因.
主要成果:
- 在75%的组织样本中发现了高水平的MET放大 (MET/CEP7比率≥5),并观察到内部损伤异质性.
- 在血中很少检测到高水平的MET放大 (17%).
- EML4-ALK 变异1 是主导的ALK 变异 (51%). 与非MET增强对应物相比,MET增强的ALK+NSCLC血显示出TP53突变,EGFR增强和MYC增强的丰富性.
结论:
- 增强MET的ALK+NSCLC经常在瘤组织中表现出高水平和异质的MET放大.
- 这个子集很少出现ALK酶域突变.
- 与TP53,EGFR和MYC变异的同时发生表明MET增强ALK+NSCLC中的瘤生物学更具侵略性.
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