Pathology oncology research: POR | |
Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790Â M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment | |
Shirong Zhang1  Lucheng Zhu2  | |
[1] Hangzhou Cancer Hospital;Nanjing Medical University | |
关键词: T790Â M; ctDNA; ARMS; ddPCR; SuperARMS; TKI resistance; | |
DOI : 10.1007/s12253-017-0286-3 | |
学科分类:生理学与病理学 | |
来源: Springer | |
【 摘 要 】
Plasma mutation detection has the advantages of non-invasiveness and accessibility. Here, we evaluated three methods, the amplification refractory mutation system (ARMS), second-generation ARMS (SuperARMS), and droplet digital PCR (ddPCR), to assess their concordance and feasibility for the detection of mutations in plasma samples. Non-small lung cancer patients with stage IIIB/IV that were resistant to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment were enrolled. Blood samples were collected within 14Â days after TKI resistance. Each sample was simultaneously assessed by the three methods. In total, 169 patients were enrolled; 54.4% were female, 72.2% were diagnosed with stage IV disease; and 97.6% had adenocarcinoma. T790Â M mutations were detected in 42 (24.8%) of the 169 samples using ARMS, one of which carried the T790Â M alone, 22 that also encoded exon 19 deletions, and 19 with L858R mutations. For the SuperARMS assay, 59 (34.9%) samples exhibited the T790Â M mutation, and 110 (65.1%) showed no detectable T790Â M mutation. ddPCR showed that 61 (36.1%) samples contained the T790Â M mutation, whereas 108 (63.9%) were not positive. T790Â M abundance ranged from 0.04% to 38.2%. The median T790Â M abundance was 0.15% for total samples and 2.98% for T790Â M mutation samples. The overall concordance was 78.7% (133/169) among ARMS, SuperARMS, and ddPCR. Compared with patients with stage III disease, patients with stage IV disease exhibited a higher T790Â M mutation detection rate (28.7% vs. 14.9% by ARMS; 37.7% vs. 27.7% by SuperARMS; and 41.8% vs. 21.3% by ddPCR). Liquid biopsy showed promise and has the advantages of non-invasiveness and accessibility. T790Â M detection based on circulating tumor DNA showed high concordance. Compared with non-digital platforms, ddPCR showed higher sensitivity and provided both frequency and abundance information, which might be important for treatment decisions.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
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RO201910252614521ZK.pdf | 619KB | download |