Virtual Library

Start Your Search

Lifeng Li



Author of

  • +

    P2.03 - Biology (ID 162)

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

      P2.03-36 - tTMB and bTMB in East Asian Lung Cancer Patients with No TKI-Related Driver Gene Mutations (ID 1183)

      10:15 - 18:15  |  Author(s): Lifeng Li

      • Abstract

      Background

      High-level TMB was shown to be correlated with the better response of immunotherapy in lung cancer patients. However, the correlation between tissue tumor mutational burden (tTMB) with the blood tumor mutational burden (bTMB) in lung cancer patients has not been fully defined, and the tTMB and bTMB of East Asian lung cancer patient harboring no TKI-related driver gene mutations remains unexplored. This study aimed to define the tTMB and bTMB in East Asian by whole-exome sequencing (WES) and panel-based sequencing, and interrogate the correlation between gene mutations and TMB in lung cancer patients with no TKI -related driver gene mutations.

      Method

      In this cohort study, 122 primary lung cancer patients without TKI-related driver gene (EGFR, ALK, ROS1, RET, BRAF, C-MET, HER2) mutations were included. tTMB and bTMB were determined by whole-exome sequencing (WES) and a targeted 451-gene panel sequencing. The correlation between any two among the WES-tTMB, the panel-tTMB and the panel-bTMB were determined, and the relationship between gene mutations and tTMB were analyzed. Statistics was performed with the SPSS 20 software.

      Result

      The mean tTMB measured by WES (WES-tTMB), the 451-gene panel (panel-tTMB) and bTMB measured by the 451-gene panel (panel-bTMB) was 4.5, 7.2 and 6.1 mutations/Mb, respectively. Significant correlation was found between panel-tTMB and WES-tTMB (Pearson r=0.76, P<0.001) or panel-bTMB (Pearson r=0.52, P<0.001), but WES-tTMB showed no correlation with panel-bTMB (Pearson r=0.189, P=0.75). The relationship between gene mutations and WES-tTMB was further explored. Patients with p53, TTN, CSMD3, ZFHX4, RYR2 , MUC16, MUC12 and USH2A gene mutations had dramatically higher tTMB (P<0.001), while no significant relationship between CDKN2A or KRAS gene mutations and TMB was identified (p>0.05). In contrast, patients harboring both KRAS and P53 mutations showed significantly higher TMB than those with either gene mutations or no mutations in both genes (P<0.001).

      tmb.jpg

      Conclusion

      Our study suggested that discrepancies exist in TMB measurement using different NGS-based detecting methods with tissue or blood sample types. The cut-off values should be determined based on detecting methods and samples types. Panel-tTMB was stronger correlation with WES-tTMB and panel-bTMB. Gene mutations were correlated with high TMB might be stronger predictors for TMB status in lung cancer patients without TKI-related driver gene mutations. Our observations provided new insights in TMB determination in East Asian lung cancer patients with NGS-based methods in various samples types and might improve the prediction of therapeutic effect and prognosis in future immunotherapy.