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Michael J Liptay



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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-15 - Validation of Tumor Organoids from Lung Adenocarcinoma as a Model of Primary Tumor Genotype (Now Available) (ID 2791)

      10:15 - 18:15  |  Author(s): Michael J Liptay

      • Abstract
      • Slides

      Background

      Tumor organoids have shown promise as a model to predict clinical treatment response in patients with certain malignancies. However, there is a paucity of data supporting the utility of tumor organoids derived from patients with non-small cell lung cancer (NSCLC). Here, we demonstrate the feasibility of establishing tumor organoids from patients with NSCLC and examine molecular fidelity of tumor organoids derived from early-stage lung adenocarcinomas relative to their primary tumors.

      Method

      140 patients who underwent lung resection for NSCLC were consented for organoid culture. Primary tumor specimens were processed to single cell suspensions and tumor cells were grown in extracellular matrix and chemically defined media. Tumor organoids and their corresponding primary tumors were evaluated by next generation sequencing for copy number and somatic alterations.

      Overall concordance between primary tumor and organoid was determined by dividing the percentage of overlapping somatic single-nucleotide variant (SNV) alterations by the total somatic SNV alterations present in both tumor and organoid model.

      Result

      A subset (n=11) of tumor organoids developed from patients with early-stage lung adenocarcinoma were assessed for molecular concordance as compared to the primary tumor within 12 weeks of establishment (approximately 2-4 passages). The tumor organoids enriched for protein coding SNV somatic mutations with an average of 6.8% overlap of all somatic SNV variants (n=2382) vs 34.8% overlap in coding SNV mutations (n=72); p<0.001. Additionally, the overlapping coding SNV mutations are further enriched in the tumor organoid as measured by allelic fraction where on average they are present at 35.3% allelic fraction as compared to 20.9% in the original tumor specimen samples tested.

      Conclusion

      Early-stage primary lung adenocarcinoma tumor organoids can be reliably generated and robustly profiled in a clinically compatible time frame. Further investigation into individual driver mutations and tumor mutational burden are underway to support this novel tumor model’s stability with sequential passaging and ability to prospectively predict therapeutic response, including strategies targeting immune checkpoint inhibition.

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