Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23983

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    P3.02-035 - Mutational Signatures and Their Association with Clinicopathological Features in Lung Adenocarcinoma of Smokers (ID 8623)

    09:30 - 09:30  |  Author(s): K. Tsuchihara
    • Abstract
    • Slides

    Background:
    Lung adenocarcinoma (LADC) harboring druggable driver oncogene such as EGFR mutation and ALK fusion can be treated with molecular-targeted drugs. These oncogene aberrations are frequently observed in LADCs of never-smoker, while LADCs of smokers often lack such druggable oncogene aberrations. Therefore, understanding mutation profile of LADCs of smokers is required to improve precision lung cancer medicine..
    
    Method:
    We analyzed mutational signatures of somatic mutations in 373 LADCs (smoker 220 cases; 59%, never-smoker 153 cases; 31%) of Japanese using whole exome sequencing data. Four mutational signatures were identified by non-negative matrix factorization and logistic regression analysis. We are now analyzing significantly mutated gene (SMG)s by MutSigCV1.5 of LADCs of smokers and associations of each signature with clinicopathological factors including histological subtype and prognosis.
    
    Result:
    Indel mutations as well as well-characterized C>A mutations were defined as mutational event more prevalent in LADC of ever-smokers than in never-smokers (P=8.76E-15 and P=0.000417 respectively). A novel set of genes were identified as a main target for indel mutations (7.4%; 22 of 296 samples), and their mutations were significantly associated with smoking and with UIP co-occurrence in their lung (P=0.0068 and P=0.037, respectively). Indel mutations in 3’-UTRs of these genes caused specific reduction in mutant transcripts, while those in coding region caused truncation of polypeptide.
    
    Conclusion:
    A novel gene set including those in 3’-UTR, would contribute to LADC development in smokers and associated with usual interstitial pneumonia, by promoting undifferentiation of tumor cells.
    
    

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  • 24022

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    P3.02-074 - Podoplanin-Positive CAF Is Associated with a Higher Number of Single Nucleotide Variants in Cancer Cells in Lung Adenocarcinoma (ID 9885)

    09:30 - 09:30  |  Author(s): K. Tsuchihara
    • Abstract

    Background:
    Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs.
    
    Method:
    Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled. First, we analyzed the clinicopathological features of the cases with podoplanin-positive CAFs, and then, we evaluated the relationship between genetic features of cancer cells (major driver mutations and the number of single nucleotide variants, or SNVs) and the presence of podoplanin-positive CAFs.
    
    Result:
    Patients with podoplanin-positive CAFs had a significantly lower 5-year recurrence-free proportion than those with podoplanin-negative CAFs (p = 0.027). We could not find any significant correlations between major genetic mutations (EGFR, KRAS, TP53, MET, ERBB2, BRAF, and PIC3CA) in cancer cells and the presence of podoplanin-positive CAFs. However, cases with podoplanin-positive CAFs had a significantly higher number of SNVs in cancer cells than the podoplanin-negative CAFs cases (median; 84 vs 37, respectively; p = 0.001). This was also detected in a non-smoker subgroup (median: 64 vs 32, respectively; p = 0.037). Multivariate analyses revealed that the number of SNVs in cancer cells was the only statistically significant independent predictor for the presence of podoplanin-positive CAFs (p = 0.044).
    
    Conclusion:
    In lung adenocarcinoma, the presence of podoplanin-positive CAFs was associated with higher numbers of SNVs in cancer cells, suggesting a relationship between accumulations of SNVs in cancer cells and the generation of a tumor- promoting microenvironment.