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Wen-Fang Tang



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    FP01 - Early Stage/Localized Disease (ID 111)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP01.03 - Genetic Predisposition for Pre-Invasive Lung Adenocarcinoma Manifesting as Ground-Glass Nodules with Family History of Lung Cancer (ID 1512)

      00:00 - 00:00  |  Author(s): Wen-Fang Tang

      • Abstract
      • Slides

      Introduction

      Lung cancer with family history have been increasing gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The predisposition of GGN with lung cancer family history remains baffling.

      Methods

      This prospective study (NCT04220268) enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, which presenting as GGN in computer tomography (CT) scans. We used extreme phenotype approach to select 50 GGN patients with a family history of lung cancer (FHLC) in one or more first-degree relatives. Blood samples were collected and sequenced by whole exome sequencing (WES) to investigate rare but potential pathogenic germline mutations with a stepwise filtering strategy including: variant quality and classification, minor allele frequency (MAF) < 0.01 in public and local database, functional prediction and family segregation.

      Results

      In total, 2325 single nucleotide variants (SNVs) and 238 frameshift mutations with MAF <0.01 were finally identified through the filter. The number of these rare, damaging germline mutations in non-smoking patients were significantly higher than those in smoking patients (Spearman’s ρ= -0.33, p=0.02). Fifty-nine SNVs and 10 frameshifts were not only rare and deleterious but also presented in more than two families. Importantly, twenty of them had been reported to be associated with higher risk or carcinogenesis of lung cancer. Two of them were validated in 126 nonoverlapping susceptibility loci for lung carcinogenesis identified by genome-wide association studies (GWAS).

      Conclusion

      Patients with GGNs and FHLC may have inheritable carcinogenesis mutations. These variants may potentially contribute to the risk of pulmonary pre-invasive adenocarcinoma susceptibility in Chinese population. Non-smoking patients with GGN probably had higher genetic predisposition than the smoking patients.

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    MA13 - Tumor Biology: Focus on EGFR Mutation, DNA Repair and Tumor Microenvironment (ID 214)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
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      MA13.09 - Heterogeneous Genomic Evolution and Immune Microenvironments in Metastatic Lung Cancer (ID 1155)

      16:45 - 17:45  |  Presenting Author(s): Wen-Fang Tang

      • Abstract

      Introduction

      The comprehensive insights into the genomic evolution and immune microenvironments of lung cancer metastasis remain unknown. Furthermore, whether non-stochastic patterns of lung cancer metastases to different sites exist is elusive.

      Methods

      We investigated the genomic evolution and immune microenvironments of paired primary-metastatic (P-M) tumors by employing multi-region whole-exome sequencing and immunohistochemistry in 179 samples from 51 lung cancer patients with metastases to the pleura, bone, adrenal gland, brain and additional lymph nodes.

      Results

      Our data revealed differences in genomic landscapes, molecular determinants, seeding patterns, and lymphocyte infiltration among different metastatic sites. Metastatic lymph nodes showed the highest P-M genomic divergence, followed by pleura, brain, bone, and adrenal gland. We identified MYC amplification as a selected event driving metastasis and associated with worse overall survival (P = 0.013). Interestingly, EGFR amplification and TP53 mutations were preferably selected in distant metastases whereas RICTOR amplification was selected in regional metastases (pleura and lymph nodes). Based on spatial tumor growth model, we demonstrated commonly late arising of metastatic seeding (61.1%) of lung cancer with quantitative evidence. However, mutation rate and timing of dissemination varied among different metastatic sites. Metastases at regional tissues were more frequently infiltrated with CD8+ tumor-infiltrating lymphocytes (TILs) than those at distant organs, among which bone metastases were merely infiltrated with CD8+ TILs. Furthermore, monoclonal and polyclonal seeding were associated with rapid and attenuated progression (P = 0.013), respectively, which supports the potential value as a prognostic predictor. Immune-heterogeneity and -homogeneity were primarily driven by arm-level and focal copy number events in primary tumors, respectively, indicating distinct mechanisms of tumor immune escape during metastasis.figure 1.jpgfigure 2.jpg

      Conclusion

      These findings implied the combinatorial role of multiple factors in shaping patterns of dissemination and advanced the clinical evaluation and intervention of lung cancer metastasis.