Author of

• 34731

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  P35 - Pathology - Genomics (ID 105)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 34760

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    P35.24 - Evaluation of an Up-To-Date Knowledge Base to Aid in Interpreting Somatic Mutations Detected in NGS Testing of Lung Cancer (ID 1633)

    00:00 - 00:00  |  Presenting Author(s): Stephanie J. Yaung
    • Abstract
    • Slides

    Introduction
    

    Routine clinical interpretation of somatic variants from next-generation sequencing (NGS) testing of cancer samples remains challenging due to evolving medical guidelines and increasingly complex multi-variant data. Results from the IASLC Global Survey on Molecular Testing in Lung Cancer presented last year at WCLC reported that 37% of those requesting and treating patients had trouble understanding molecular test results (Smeltzer et al., JTO 2019). We assessed the ability of a CE-IVD somatic variant interpretation tool, NAVIFY® Mutation Profiler*, to provide accurate and timely clinical content to aid in the interpretation of somatic variants in 904 lung cancer samples from publicly available datasets such as The Cancer Genome Atlas (TCGA).

    Methods
    

    469 lung adenocarcinoma (LUAD), 325 lung squamous cell carcinoma (LUSC), and 110 small cell lung cancer (SCLC) cases were analyzed. We utilized whole exome results of TCGA LUAD and LUSC studies from the Multi-Center Mutation Calling in Multiple Cancers project, which completed consensus calling of single nucleotide variants and indels (Ellrott et al., Cell Systems 2018). Whole genome results for SCLC samples were obtained from the cBioPortal U Cologne study (George et al., Nature 2015). The open-access Mutation Annotation Format (MAF) files that store variant calls were lifted over to human reference genome GRCh38 then converted to individual Variant Call Format (VCF) files per sample. We uploaded the VCF files to NAVIFY Mutation Profiler to interpret actionable mutations according to a highly curated and regularly updated knowledge base (Roche Content v2.13.0 released December 6, 2019).

    Results
    

    Over 20,000 genes with a total of 363,921 somatic mutations were assessed with NAVIFY Mutation Profiler, which reports tier classifications of variants based on consensus recommendations from AMP, ASCO, CAP, and ACMG. Of all lung cases, 86% had variants of strong (Tier I-A or I-B) or potential (Tier II-C or II-D) clinical significance. Tier I classifications, supported by robust clinical evidence, were found in 24% of cases, mainly in lung adenocarcinoma cases where there are known targetable mutations. Furthermore, the tool identified appropriate tier classifications by geographic region in accordance with medical guidelines.

    Conclusion
    

    In order to benchmark against other annotation tools, we assessed NAVIFY Mutation Profiler with open-access tumor-normal whole exome or genome data. Since fusions or copy number variants are also present in these samples, this study likely underestimates the proportion of cases with clinically significant mutations. Nevertheless, we found a higher percentage of samples with potentially actionable annotation than other previously published methods.

    _{* This product is not for diagnostic purposes in the United States and is not commercially available in the United States.}

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