Osteosarcoma (OS) is the primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here we present the first large cohort of 121 OS patients from Shanghai General Hospital (SGH-OS Cohort), using hybrid-capture DNA sequencing, array-based DNA copy number, DNA methylation profiling and mRNA sequencing. Through integrating multi-omics data, we obtained a comprehensive genomic, epigenomic and transcriptomic landscape of OS and uncovered four distinct molecular subtypes with varied oncogenic factors. Moreover, we explored the diversity of clinical outcomes and the subtype-based targeted intervention that may influence OS clinical management. Our study provides a valuable insight into the biology of this disease, and a strong foundation of future precision medicine for each subtype that will eventually improve overall survival of osteosarcoma.
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HRA003260.xlsx