Clini Cancer Res:SMARCA4突变可预测肺癌患者预后

2020-07-26 QQY MedSci原创

SMARCA4突变是非小细胞肺癌(NSCLC)中最常见的复发性变异之一,但其与其他基因组异常的关系和临床影响尚未确定。本研究拟总结SMARCA4突变在NSCLC中的特征。

背景:
 
SMARCA4突变是非小细胞肺癌(NSCLC)中最常见的复发性变异之一,但其与其他基因组异常的关系和临床影响尚未确定。

方法:

为了总结SMARCA4突变在NSCLC中的特征,Schoenfeld等分析了凯特琳癌症中心治疗的携带SMARCA4突变的NSCLC患者的基因组、蛋白表达和临床预后数据。

结果:

在4813位肿瘤患者中,有407位(8%)患者为SMARCA4突变型肺癌。研究人员将SMARCA4突变分成了两类:1型突变(截短突变、融合和纯合缺失)和2型突变(错义突变)。蛋白表达缺失与1型突变相关(81% vs 0%,p<0.001)。与SMARCA4野生型肿瘤相比,这两类突变与KRAS、STK11和KEAP1突变共同出现的频率更高(p<0.001)。

在转移性NSCLC患者中,SMARCA4变异与患者生存期更短相关,其中1型变异与存活时间最短相关(p<0.002)。相反,研究人员发现用免疫检查点抑制剂治疗与SMARCA4突变型肿瘤患者预后改善有关(p=0.01),其中1型突变患者对ICIs的反应性最好(p=0.027)。

结论:

SMARCA4变异可被分成两类临床相关的基因组类别,它们与不同水平的蛋白表达以及不同的预后和治疗意义相关。这两类突变均可与KEAP1、STK11和KRAS突变同时发生,并可独立预示预后不良。虽然与不良预后有关,但SMARCA4突变型肺癌可能对免疫治疗更敏感。

原始出处:

Adam J Schoenfeld,et al. The Genomic Landscape of SMARCA4 Alterations and Associations with Outcomes in Patients with Lung Cancer. Clinical Cancer Research. July,2020.DOI: 10.1158/1078-0432.CCR-20-1825

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    2020-07-28 江川靖瑶

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