Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

Z. Huo



Author of

  • +

    ORAL 30 - Community Practice (ID 141)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Community Practice
    • Presentations: 1
    • +

      ORAL30.05 - Clinical Implementation of the NextDaySeq Lung Panel for Identification of Clinically Actionable Variants in Non-Small Cell Lung Cancer (ID 3099)

      17:28 - 17:39  |  Author(s): Z. Huo

      • Abstract
      • Presentation
      • Slides

      Background:
      Molecular testing-directed targeted therapies are transforming treatment paradigms for non-small cell lung cancer (NSCLC). The clinical application of next-generation sequencing (NGS) technologies has offered a more comprehensive understanding of the mutational landscape. Efforts have been made in the past three years in the Department of pathology at the Peking Union Medical College Hospital, to adopt NGS in the clinical setting allowing rapid and reliable detection of actionable mutations that facilitate therapeutic decision making and disease prediction for at-risk patients

      Methods:
      The NextDaySeq Lung panel on Ion Torrent[TM] System and DanPA bioinformatics pipeline have been implemented in our clinical laboratory. The workflow employs novel chemistry in library preparation and innovation in informatics, which allows a 48-hour turnaround from FFPE samples to identification of variants with demonstrated clinical importance. The test sequences 16 exons in EGFR, KRAS, BRAF, PIK3CA, ALK, DDR2 and PDGFRA, covering 82 well recognized hotspots. The end-to-end test performance has been established with analytical sensitivity and specificity as well as the assay’s repeatability and reproducibility. Up to date, more than 200 samples have been examined including both lung adenocarcinoma and lung squamous carcinoma. To characterize the analytical performance, the NGS results have been compared with Sanger sequencing that covers the same exons, as well as QPCR assays (CFDA approved IVD kits) that cover a majority of hotspots within these exons.

      Results:
      Analysis of 200 cases indicated 100% concordance for reportable variants mutually covered in both NGS and QPCR assays. Eight cases reported at least one additional potentially clinically relevant variant, for example, in EGFR and PIK3CA, that would not have been identified in previously implemented QPCR assays. The mutation rates reported in 200 cases ranged from 2.4% to 84.3% according to DanPA analysis, while Sanger sequencing failed to detect variants in 32 cases with mutation rates lower than 20%. The Indel analysis had been a challenge for previous NGS tests in the lab, and the current test resolved the issue with the DanPA pipeline, demonstrating 100% PPV and NPV values compared with QPCR, and Sanger when mutation rates higher than 20%. Additionally, we documented multiple cases that carry double and triple mutations, which were rare in lung cancer, and also identified several novel mutations.

      Conclusion:
      Therefore, we reported the validation of NextDaySeq Lung panel for high throughput detection of mutations in NSCLC, and the development of a wet-bench and informatics workflow enabling timely and informative molecular diagnosis. The implementation of the test offers significantly improved information benefit over previous tests, and holds the promise to impact patient management.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.