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Clone evolution and genomic alteration analysis of osteosarcoma and matched lung metastasis.

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11032Background: Lung metastasis (LM), as the most common metastatic site, is the main reason resulting in treatment failure and death of osteosarcoma (OS). But there was no report about the… Click to show full abstract

11032Background: Lung metastasis (LM), as the most common metastatic site, is the main reason resulting in treatment failure and death of osteosarcoma (OS). But there was no report about the clone evolution and genomic alteration in the process of LM of OS. Methods: Multiregion whole-genome sequencing and whole-exome sequencing were performed on ten patients with primary OS and matched lung metastatic tumors. A set of high confident somatic nucleotide variants (SNV), small insertion and deletion (indel) and copy number variation (CNV) in each sample were identified, then the n-dimensional Bayesian Dirichlet process was applied to define the constituent mutation clusters as clone or subclone. Neoantigen prediction and HLA typing were performed using NetMHC3.0 and POLYSOLVER algorithm, respectively. Results: There were diversified metastatic progression during lung metastasis of OS including linear evolution (7/10) and parallel evolution (3/10), and metastasis-to-metastasis spread was also found in a patien...

Keywords: evolution genomic; evolution; metastasis; clone evolution; genomic alteration; lung metastasis

Journal Title: Journal of Clinical Oncology
Year Published: 2017

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