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MET Y1003S点突变显示对肺腺癌患者中克唑替尼的敏感性

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MET Y1003S点突变显示对肺腺癌患者中克唑替尼的敏感性
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Abstract
Objectives
MET amplification or MET exon 14 skipping site mutation can be treated with crizotinib in non-small cell lung cancer patients. Y1003 is a binding site for E3 ubiquitin ligase, which is critical for MET degradation. Here we show an adenocarcinoma patient with Y1003S mutation and she got tumor remission after crizotinib treatment.

Materials and Methods
A 61-year-old never-smoking female was admitted to our hospital due to increased carcino-embryonicantigen. Positron emission tomography (PET)-CT showed enlargement of bilateral cervical, left supraclavicular and multiple mediastinal lymph nodes. PET-CT also showed stripe in the left upper lobe. Adenocarcinoma cells were found from biopsy on her left supraclavicular lymph nodes. We detected cell-free circulating tumor DNA (ctDNA) from peripheral blood and identified a MET Y1003S mutation by next generation sequencing technology. Y1003 mutations predicted to be similar to MET exon 14 skipping in functionality based on the literature. After an extensive discussion of treatment options, the patient opted to treatment with crizotinib, a small-molecule dual inhibitor of the MET and ALK.

Results and Conclusion
Dramatic response was observed within 1 months of treatment, which lasted more than 10 months. Chest CT scans revealed significant improvement of the lung focus and decrease in size of the lymph nodes lesions, meeting RECIST partial response criteria (−30%). Y1003 alterations may be diverse mutations and sensitive to MET inhibitors.

Keywords
METY1003MutationCrizotinibMET inhibitorNon-small cell lung cancer

目标
可以在非小细胞肺癌患者中用克唑替尼处理MET扩增或MET外显子14跳跃位点突变。 Y1003是E3泛素连接酶的结合位点,其对MET降解至关重要。在这里,我们显示具有Y1003S突变的腺癌患者,并且在克唑替尼治疗后她得到肿瘤缓解。

材料和方法
由于癌胚胎抗原增加,一名61岁的从不吸烟女性入院。正电子发射断层扫描(PET)-CT显示双侧颈部,左锁骨上和多个纵隔淋巴结肿大。 PET-CT在左上叶也显示出条纹。从左锁骨上淋巴结活检中发现腺癌细胞。我们从外周血中检测到无细胞循环肿瘤DNA(ctDNA),并通过下一代测序技术鉴定出MET Y1003S突变。基于文献,Y1003突变预测与MET外显子14相似,跳过功能性。在对治疗方案进行广泛讨论后,患者选择使用克里唑蒂尼(一种MET和ALK的小分子双重抑制剂)进行治疗。

结果和结论
在治疗后1个月内观察到显着反应,持续超过10个月。胸部CT扫描显示肺部焦点明显改善,淋巴结病变大小减小,符合RECIST部分反应标准(-30%)。 Y1003改变可以是多种突变并且对MET抑制剂敏感。

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