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Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment

  • Original Article
  • Published:
Pathology & Oncology Research

A Correction to this article was published on 08 June 2018

This article has been updated

Abstract

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 14 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. T790 M mutations were detected in 42 (24.8%) of the 169 samples using ARMS, one of which carried the T790 M alone, 22 that also encoded exon 19 deletions, and 19 with L858R mutations. For the SuperARMS assay, 59 (34.9%) samples exhibited the T790 M mutation, and 110 (65.1%) showed no detectable T790 M mutation. ddPCR showed that 61 (36.1%) samples contained the T790 M mutation, whereas 108 (63.9%) were not positive. T790 M abundance ranged from 0.04% to 38.2%. The median T790 M abundance was 0.15% for total samples and 2.98% for T790 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 T790 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. T790 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.

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Change history

  • 08 June 2018

    The affiliation of first author (Lucheng Zhu) should be Department of Oncology, Hangzhou Cancer Hospital and Department of Oncology, Hangzhou First People’s Hospital, Nanjing Medical University.

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Acknowledgements

This study was supported by grants from Projects of Medical and Health Technology in Zhejiang Province (WKJ-2J-1532), the Zhejiang Provincial Natural Science Foundation (LY15H160010), National Natural Science Foundation (81773242), and National Natural Science Foundation (81602671).

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Correspondence to Shirong Zhang or Shenglin Ma.

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Supplementary Figure S1

T790 M abundance analyses stratified by ARMS (A) and SuperARMS (B). Each dot in scatter plot represent T790 M abundance of each patient. Red line represents 1% abundance (GIF 9 kb)

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Zhu, L., Zhang, S., Xun, Y. et al. Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment. Pathol. Oncol. Res. 24, 843–851 (2018). https://doi.org/10.1007/s12253-017-0286-3

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