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Lu Zhang



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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-121 - Genomic Profiling of Pulmonary Lymphoepithelioma-Like Carcinoma (ID 13877)

      16:45 - 18:00  |  Author(s): Lu Zhang

      • Abstract
      • Slides

      Background

      Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct type of primary lung cancer which is characterized by Epstein-Barr virus (EBV) infection. Only a few hundred cases have been reported since its discovery in 1987. Due to its extreme rareness, its genomic landscape remains elusive. In this study, we performed targeted ultra-deep sequencing to interrogate the genomic profile and tumor mutation burden of 10 patients with pulmonary LELC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Ten patients with advanced pulmonary LELC patients were enrolled. Tissue biopsy samples were subjected to targeted sequencing with an average sequencing depth of 1,000x, using a panel consisting of 295 cancer-related genes, spanning 2.02Mb of human genome. TMB was calculated as the ratio of number of mutations to the size of coding region of the panel, excluding copy number variations, fusions and large genomic rearrangements.

      4c3880bb027f159e801041b1021e88e8 Result

      We enrolled 10 patients (4 males and 6 females) with advanced pulmonary LELC and a median age of 60. Eight of them are non-smokers and 2 are smokers. Collectively, we identified 65 somatic mutations spanning 52 genes, including 33 SNVs, 3 insertions or deletions (INDELs) and 29 copy-number amplifications (CNAs). No mutation in classic NSCLC driver gene was identified, in an agreement of published data. The most frequently mutated genes were TP53, FGFR3, FGFR4, FGFR19 and CCND1, occurring in 30% (3/10) patients followed by KIT and KMT2D, occurring in 20% (2/10) patients. Interestingly, 7 patients had mutations in epigenetic regulators, such as DNA methyltransferase and chromatin remodelers. Pathway analysis also revealed an enrichment of genes participating in chromatin remodeling and organization. Next, we compared the genomic profile of pulmonary LELC with nasopharyngeal carcinoma and EBV positive gastric cancer mutation profiles obtained from TCGA, and revealed similarity with both of them. Patients in this cohort had a median TMB of 3.75/Mb (ranged from 1.25/Mb to 10/Mb), which is significantly lowered than lung adenocarcinomas. All patients had PD-L1 overexpression; 4 of them with PD-L1 expression in greater than 50% of tumor cells and the remaining 6 patients had PD-L1 expression between 5%-49% of tumor cells.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this study, we elucidated a distinct genomic landscape associated with pulmonary LELC with no classic NSCLC driver mutation but an enrichment of mutations in epigenetic regulators. The observation of high expression of PD-L1 and lack of canonical druggable driver mutation raises the potential of immunocheckpoint blockade therapy for LELC.

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