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Apostolos Nakas



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    P2.06 - Mesothelioma (ID 170)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.06-11 - MEDUSA: Phylogenetic Analysis of Mesothelioma Tumours by Multiregional Sampling, Whole Exome Sequencing, and Copy Number Analysis (ID 921)

      10:15 - 18:15  |  Author(s): Apostolos Nakas

      • Abstract

      Background

      The Mesothelioma evolution: Drugging somatic alterations (MEDUSA) project aims to investigate the genomic evolution and heterogeneity of malignant pleural mesothelioma and identify genomic changes early in mesothelioma evolution that can be targeted by drugs. For 20 malignant pleural mesothelioma patients, we have analysed the exomes of at least four regions of the tumour and paired whole blood.

      Method

      Using paired tumour-normal analysis with the software Sequenza, we have called copy number alterations specific to the tumour, and used the software Tumult to reconstruct a phylogeny of the tumour for each of the 20 patients.

      Result

      We show that mesothelioma shows extensive heterogeneity in copy number changes, and accumulates typically between 100-200 copy number gains and losses while evolving in a branching pattern. We identify and validate copy number alterations that occur truncally, early in the evolution of the tumour, and are recurrent across patients, including homozygous loss of CDKN2A and MTAP in 4/20 patients, heterozygous loss of MTOR in 6/20 patients and heterozygous loss of BAP1 in 4/20 patients. Losses of these key genes are observed in some other patients, but only in a subset of regions, suggesting that they have occurred later in the evolution of the tumour compared to truncal changes.

      Conclusion

      As truncal changes are likely to be present throughout the tumour, identifying them highlights potential Achilles’ heels for drug targeting and treatment.