(P 021) DISTINCT GENOMIC FEATURES BETWEEN OSTEOSARCOMAS FIRSTLY METASTASING TO BONE AND TO LUNG

Objective: Osteosarcoma initially metastasing to bone only shows distinct biological features compared to osteosarcoma that firstly metastasizes to the lung, which suggests us underlying different genomic pathogenetic mechanism. However, related-study is lacking.

Methods: We analyzed whole-exome sequencing (WES) data for 38 metastatic osteosarcoma patients with different relapse patterns. Multiplex Immunohistochemistry was also applied to investigate the immune- microenvironment. We tried to redefine disease subclassifications for osteosarcoma based on genetic alterations to guide treatment strategies, and we correlated these genetic profiles with clinical treatment courses and prognosis to elucidate potential evolving cladograms.

Results: We investigated whole-exome sequencing of 12/38 patients with high-grade osteosarcoma (31.6%) with initial bone metastasis (group A) and 26/38 (68.4%) with initial pulmonary metastasis (group B), of whom 15/38 (39.5%) had paired samples of primary lesions and metastatic lesions for these two cohorts with different relapse patterns. We found that osteosarcoma in group A mainly carries single-nucleotide variations while those in group B mainly exhibits structural variants. Additionally, osteosarcoma in group A displayed better immunogenicity, including a higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures in tumor microenvironment.

Conclusion: Osteosarcoma with different relapse patterns has distinct genomic landscapes. This study suggests that osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases; immunotherapy is a promising therapeutic option for this group of patients.

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