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Y. Chen

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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      202P - The clone evolutionary landscape and genomic characteristics of osteosarcoma and lung metastasis (ID 204)

      12:30 - 13:00  |  Author(s): Y. Chen

      • Abstract
      • Slides

      Tumor metastasis is still the main cause of cancer related mortality, so it is important to identify the key molecules in each step of tumor metastasis and develop new strategies for prevention and control of tumor metastasis. Osteosarcoma (OS) is a primary malignant bone tumor that has a high potential to metastasize to lungs. Few consistent clinically actionable mutations have been reported and no further improvements have been made in the last decades regarding survival. Therefore, biomarkers prognosticating for overall survival or the development of lung metastases in patients with OS may improve personalized care. The study of our aim is to investigate harbor distinct genetic alterations beyond those observed in primary tumors.

      Next-generation sequencing (NGS)-based 381 genes panel assay were performed on ten patients with primary OS and matched lung metastatic tumors. A set of high confident SNV, small insertion and indel and CNV in each sample were identified.

      There were diversified metastatic progression during lung metastasis of OS including parallel evolution (6/10) and linear evolution (4/10), and metastasis-to-metastasis spread was also found in two patients with multiple metastasis. Multiple novel significantly mutated genes were identified, including CREBBP, LRP1B, MAP3K1 and LRP1B in lung metastases, SETD2, GNAS, and H3F3A in primary tumors, and CDKN2A in both. Copy number analysis indicated recurrent CNAs, including NFKBIA gain, MCL1 gain, and MYC gain in lung metastases, AMER1 loss, CTNNB1 gain in primary tumors, and CDKN2B gene family loss in both. Furthermore, phylogenetic analyses revealed that paired primary tumors and metastases underwent parallel evolution with few ubiquitous clonal mutations, suggesting that OS metastases are likely to be derived from primary tumors at a very early stage of their evolution.

      The evolution of primary and metastatic tumors were very complex. Our findings strongly support a parallel evolution model of primary and metastatic tumors. Moreover, the much higher mutation load and significantly mutated genes that are specifically associated with lung metastases may provide immune checkpoint inhibitor and target therapeutic insight for OS.

      Clinical trial identification:

      Legal entity responsible for the study:
      Jinhuo Lai

      Has not received any funding

      All authors have declared no conflicts of interest.

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