A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma
A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma
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DOI：
10.1016/j.jtho.2016.05.035
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发表时间：
2016-10-01
影响因子：
20.4
通讯作者：
Gadgeel, Shirish
中科院分区：
文献类型：
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作者：
Reckamp, Karen L.;Melnikova, Vladislava O.;Gadgeel, Shirish
在大约60%接受EGFR酪氨酸激酶抑制剂治疗的NSCLC患者中，耐药性是通过获得EGFR T790M突变而产生的。我们的目的是证明对尿液和血浆标本中EGFR突变进行高灵敏度和定量的下一代测序分析是可行的。方法：使用短足迹突变富集下一代测序法来调查TIGER-X （NCT01526928）患者尿液或血浆标本中的EGFR激活突变和T790M耐药突变，TIGER-X是罗西莱替尼在先前治疗的EGFR突变阳性晚期NSCLC患者中的1/2期临床研究。结果：63例患者中，60例有可评估的组织标本。当组织结果作为参考时，尿液中EGFR突变检测T790M的敏感性为72%（47例中34例），L858R的敏感性为75%（16例中12例），外显子19缺失的敏感性为67%（42例中28例）。对于符合推荐体积90 ~ 100 mL的标本，T790M的灵敏度为93%（14个标本中的13个），L858R的灵敏度为80%（5个标本中的4个），外显子19缺失的灵敏度为83%（12个标本中的10个）。血浆中EGFR突变检测的灵敏度也相当：T790M为93%（41例中38例），L858R为100%（17例中17例），第19外显子缺失为87%（39例中34例）。尿液和血浆检测共同确定了另外12例t790m阳性病例，这些病例要么无法通过组织检测检测到，要么检测不足。在接受罗西替尼治疗期间监测的9例患者中，在第21天观察到尿T790M水平迅速下降。结论：来自非小细胞肺癌肿瘤的DNA可以在尿液和血浆中高灵敏度检测到，从而可以通过这些无创“液体活检”样本进行诊断检测和治疗反应监测。(C) 2016年国际肺癌研究协会。Elsevier Inc.出版。
Introduction: In approximately 60% of patients with NSCLC who are receiving EGFR tyrosine kinase inhibitors, resistance develops through the acquisition of EGFR T790M mutation. We aimed to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations from urine and plasma specimens is feasible.Methods: Short footprint mutation enrichment next generation sequencing assays were used to interrogate EGFR activating mutations and the T790M resistance mutation in urine or plasma specimens from patients enrolled in TIGER-X (NCT01526928), a phase 1/2 clinical study of rociletinib in previously treated patients with EGFR mutant-positive advanced NSCLC.Results: Of 63 patients, 60 had evaluable tissue specimens. When the tissue result was used as a reference, the sensitivity of EGFR mutation detection in urine was 72% (34 of 47 specimens) for T790M, 75% (12 of 16) for L858R, and 67% (28 of 42) for exon 19 deletions. With specimens that met a recommended volume of 90 to 100 mL, the sensitivity was 93% (13 of 14 specimens) for T790M, 80% (four of five) for L858R, and 83% (10 of 12) for exon 19 deletions. A comparable sensitivity of EGFR mutation detection was observed in plasma: 93% (38 of 41 specimens) for T790M, 100% (17 of 17) for L858R, and 87% (34 of 39) for exon 19 deletions. Together, urine and plasma testing identified 12 additional T790M-positive cases that were either undetectable or inadequate by tissue test. In nine patients monitored while receiving treatment with rociletinib, a rapid decrease in urine T790M levels was observed by day 21.Conclusions: DNA derived from NSCLC tumors can be detected with high sensitivity in urine and plasma, enabling diagnostic detection and monitoring of therapeutic response from these noninvasive "liquid biopsy" samples. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc.