Author of

• 30943

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  P2.04 - Immuno-oncology (ID 167)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 31021

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    P2.04-67 - Comparative Analysis of TMB and Mutations by Comprehensive Genomic Profiling (TSO500) in FFPE NSCLC Samples (ID 2106)

    10:15 - 18:15  |  Author(s): Lotte Moens
    • Abstract

    Background
    

    Precision oncology for NSCLC involves an increasing number of targeted drugs and immunotherapy options. Comprehensive genetic profiling has been used in clinical studies to assess predictive biomarkers and mutation patterns, i.e. tumor mutation burden (TMB) associated with checkpoint therapy response. However, limited access to broader sequencing approaches, associated complex bioinformatic pipelines and issues with cross-platform reproducibility remain important hurdles for routine molecular pathology.

    Method
    

    Here we have used the novel TSO500 gene panel (523 genes, 1.95 Mb) on the NextSeq platform (Illumina) to analyze representative surgical FFPE NSCLC specimens (n=50). Detected mutations were evaluated in comparison to matched results from routine diagnostic sequencing based on a custom 18-gene HaloPlex panel (Agilent). Obtained TMB-scores will be compared to data from analysis with the FoundationOne CDx assay (work in progress).

    Result
    

    All 50 samples passed the pre-set QC filters. We found a wide range of TMB-values (0.79 to 610 non-synonymous mutations per Mb) with a median score of 5.6 mut/Mb (Figure 1). EGFR positive cases were found in the lower TMB range, while the remaining adenocarcinoma and squamous cell carcinomas were evenly distributed across the TMB spectrum. All known variants (n=105) from routine sequencing could be detected in the TSO500 data set (Illumina and in-house bioinformatic pipeline) with similar variant allele frequencies (r= 0.76).

    Conclusion
    

    Variant calling with regard to NSCLC hot-spot mutations seems to be robust, but the precision and performance of TSO500 outside clinical hot-spot regions remain to be established. The distribution of TMB scores in our series of NSCLC seems to be consistent with previously published data and concordance to results with FoundationOne CDx will be presented.