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- W2890796531 abstract "11029 Background: Osteosarcoma (OS) is a primary malignant bone tumor that has a high potential to metastasize to lungs. Recent studies have characterized somatic mutations of primary OS tumors. Nevertheless, lung metastases of OS are poorly studied, and whether they harbor distinct genetic alterations beyond those observed in primary tumors is largely unknown. Methods: We performed whole-exome sequencing (WES) of matched primary tumors and lung metastases in a cohort of 15 OS patients. Somatic single nucleotide variations (SNV) and copy number alterations (CNA) were analyzed to characterize the genomic and evolutionary landscape of metastatic OS. Results: Compared to matched primary tumors, lung metastases exhibited higher transversion rate for base substitution, and poor overlap ( < 10%) of genetic alterations was observed between primary and metastasis tumors. Multiple novel significantly mutated genes were identified, including ZNF717 in lung metastases, SPDYE1 in primary tumors, and CRIPAK in both. Copy number analysis indicated recurrent CNAs, including NEURL1B deletion and FLG amplifications in lung metastases, GSTT1 deletion in primary tumors, and CEACAM gene family deletion 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. Conclusions: This study for the first time provides important evidence that OS metastases harbor distinct genetic alterations compared with primary tumors. Our findings strongly support a parallel evolution model of primary and metastatic tumors. Moreover, several novel CNAs and significantly mutated genes that are specifically associated with lung metastases may provide future therapeutic insight for OS." @default.
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- W2890796531 date "2017-05-20" @default.
- W2890796531 modified "2023-09-26" @default.
- W2890796531 title "The genomic and evolutionary landscape of osteosarcoma progression and lung metastasis." @default.
- W2890796531 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.11029" @default.
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