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

  • 34749

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    P35.26 - Comparative Genomic Profiling of Lung Adenocarcinoma in Self-Reported Asian and White Patients, a Propensity Matched Study of 1400 Samples (ID 1904)

    00:00 - 00:00  |  Presenting Author(s): Jian Zhou
    • Abstract

    Introduction
    

    Lung adenocarcinomas (LUADs) from Asian ancestry are reported to have different genomic architectures compared with LUADs from White patients. However, due to lack of available cases, few studies controlled the clinical attributes during comparisons of the genomic alterations. GENIE database, which consists of 9699 lung adenocarcinoma samples with clinical annotations, provides the chance of performing propensity score matching with abundant cases.

    Methods
    

    Samples sequenced with panels covering all OncoKB actionable genes were accessed from GENIE database. Propensity score analysis (nearest neighbor matching method, 1:4) was applied to Asian vs White cohorts using age, sex, sample type (primary/metastasis), enrolling center and sequencing assay. Mutation count, copy number alterations were compared using an MSK subset because the mutation count correlates with TMB in those panels. Fisher’s exact test and FDR adjust method were used for comparisons.

    Results
    

    280 samples from Asian patients and 1120 from White patients were included after propensity matching. Comparative mutation analysis revealed Asian cohort displayed higher EGFR and PIK3CA mutations (q-value <0.05). White cohort displayed higher KRAS, STK11, KEAP1 and SMARCA4 mutations (q-value <0.05). Copy number analysis revealed that TERT amplification is higher in Asian cohort (q-value <0.01). In both cohorts, EGFR alteration has a tendency of mutual exclusivity with KRAS, ROS1 and ALK alterations (q-value <0.05). A subset of the cohort using MSK data showed that White cohort has higher tumor mutation count (p<0.001) while Asian cohort has higher copy number variation (p<0.001).

    

    Conclusion
    

    This propensity-matched study elucidated different gene mutation and copy number variation spectrums between Asian and White LUAD samples. However, both cohorts showed an overlapping tendency of mutual exclusivity. These results may contribute to the studies of LUAD biological development and pharmaceutical researches.