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Xun Shi



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-43 - Next-Generation Sequencing in the Exploration of Genetic Heterogeneity for Lung Adenocarcinoma Patients with EGFR Activating Mutations (ID 11194)

      16:45 - 18:00  |  Author(s): Xun Shi

      • Abstract
      • Slides

      Background

      Increasing evidence leads to a ratiocination that genetic heterogeneity of the lung adenocarcinoma patients with sensitive EGFR mutations may impact clinical responses and outcomes to EGFR-TKIs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed targeted NGS with a gene panel covering 416 cancer-related genes to profile genetic characteristics of 69 lung adenocarcinoma patients with activating EGFR mutations and assessed the contribution of targeted NGS to exploration of genetic heterogeneity of such cohort.

      4c3880bb027f159e801041b1021e88e8 Result

      We detected total 200 actionable genetic alterations (mean 2.9 variations per patient, range: 1-7 variations) in tumor DNA and 140 actionable genetic alterations (mean 2.0 variations per patient, range: 0-5 variations) in matched plasma ctDNA, respectively. The concurrent genes with the highest mutation rate were TP53 (observed in 72.5% patients), other uncommon EGFR mutations (observed in 21.7% patients), EGFR amplification (observed in 20.3% patients), RB1 (observed in 10.1% patients), PIK3CA (observed in 7.2% patients), and MYC (observed in 5.8% patients). NGS provides EGFR mutation detection in plasma with a test sensitivity of 88.2% and specificity of 100.0%. Novel mutations potentially related to primary drug resistance were identified including: CDC73, SMAD4, and CTNNB1 missense mutations; RB1, ARID1A, ARID2, DNMT3A, STK11, and ATR frameshift indel; CDKN2B-PATA31D1, NFKBIA-OR11H12 fusion gene; PRKCI, CCNE1, MCL1, ARAF copy number gain; RB1 loss. The pathways analysis showed that unique pathways in the primary resistant cohort included: 1) immune related pathways: Toll-like receptor signaling pathway, T cell receptor signaling pathway; 2) epithelial-mesenchymal transition (EMT) related pathways: TGF-beta signaling pathway; 3) downstream pathway of EGFR: PIK3CA/AKT/mTOR signaling pathway; 4) cell function related pathways: Mismatch repair pathway, AMPK signaling pathway, TNF signaling pathway, Notch signaling pathway, and Transcriptional misregulation in cancer.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, we note the complexity and heterogeneity of activating EGFR-mutant lung adenocarcinoma that may confer primary resistance to EGFR TKI using NGS platform. This study highlights the advantage of the NGS than traditional methods on testing EGFR mutations, enabling further refinement in sub-classification for the improved personalization of lung cancer treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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