Background: Non-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies.
Materials and methods: We performed a targeted rearrangement assay on 54 NSCLCs across all stages that were from patients who were never smokers and did not have driver mutations. Because MET exon 14 skipping was the most frequent alteration found, we surveyed the results for MET exon 14 skipping at Massachusetts General Hospital (MGH) since the inclusion of this alteration into our current molecular profiling panel.
Results: In a cohort of 54 never-smokers with lung cancers that were wild-type for known driver mutations, MET exon 14 skipping was the most frequently recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via our next-generation sequencing (NGS) and NGS-rearrangement panels showed an additional 16 cases of MET exon 14 skipping, for an overall estimated frequency of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the MET inhibitor crizotinib is also described.
Conclusion: MET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition.
Implications for practice: MET exon 14 skipping occurs with an approximately 5% frequency in NSCLC and is seen in both squamous and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping should be performed on all lung cancers because this is a targetable alteration.
摘要
背景. 非小细胞肺癌 （NSCLC） 包含的特异性遗传改变可能对靶向疗法高度敏感。
材料与方法. 我们对 54 例不同疾病分期且从不吸烟、无驱动突变的 NSCLC 患者进行了靶基因重排检测。由于 MET 外显子 14 跳读是最常见的改变, 因此我们当前的分子谱板纳入了这一改变。本研究特别调查了麻省总院 （MGH） 的 MET 外显子 14 跳读结果。
结果. 在 54 例从不吸烟的已知驱动突变野生型肺癌患者的队列中, MET 外显子 14 跳读是最常见的重复改变, 见于 10 例癌症患者 （19%）。MGH 使用我们的第二代测序技术 （NGS） 和 NGS 重排板发现了另外 16 个 MET 外显子 14 跳读病例, 总的预估频率为 5.6%。本文还介绍了 MET 外显子 14 跳读患者接受 MET 抑制剂克唑替尼治疗的临床案例。
结论. MET外显子14跳读可以作为NSCLC患者基因改变的靶标。存在这些改变的患者可能对MET抑制治疗有较好的反应。The Oncologist 2016;21:481–486
对临床实践的提示: NSCLC 患者中的 MET 外显子 14 跳读发生率约为 5%, 并且在鳞癌和腺癌组织学中均可见到。存在 MET 外显子 14 跳读的癌症患者可能对 MET 抑制剂治疗反应良好。由于 MET 外显子 14 跳读可以作为基因改变的靶标, 因此对所有肺癌患者都应进行 MET 外显子 14 跳读的分子检测。
Keywords: Lung cancer; MET exon 14 skipping; Targeted therapy.
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