OBJECTIVES MET c-Cbl binding site mutations constitute about 2 % of MET exon 14 alterations in lung cancer. Preclinical data suggests regarding these mutations as functional analogs of MET exon 14 skipping mutations, but clinical validation is lacking. RESULTS We report the case of a patient with metastastic lung adenocarcinoma harboring a c-Cbl binding site alteration and demonstrate clinical, radiological and metabolic response to crizotinib with a PFS of 10.6 months. As escape mechanism, a typical MET resistance mutation could be identified. CONCLUSION MET c-Cbl binding site mutations should be regarded as a distinct subtype of MET exon 14 alterations. Patients with lung cancer harboring such mutations should be offered targeted therapy.

中文翻译：

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对克唑替尼的临床反应和肺腺癌中存在MET c-Cbl结合位点突变的耐药性的出现。

目的MET c-Cbl结合位点突变构成肺癌中MET外显子14改变的2％。临床前数据表明，将这些突变视为MET外显子14跳过突变的功能类似物，但缺乏临床验证。结果我们报告了一个转移性肺腺癌患者的c-Cbl结合位点改变的病例，并证明了对crizotinib的临床，放射学和代谢反应，PFS为10.6个月。作为逃逸机制，可以确定典型的MET抗性突变。结论MET c-Cbl结合位点突变应被视为MET外显子14改变的独特亚型。携带此类突变的肺癌患者应接受靶向治疗。