Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets
書誌事項
- 公開日
- 2022-06-15
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s41467-022-30453-x
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title> <jats:p> The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analysis of 2,138 sarcomas representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations are in cell cycle control and <jats:italic>TP53</jats:italic> , receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations include <jats:italic>TERT</jats:italic> amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varies between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response. </jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 13 (1), 3405-, 2022-06-15
Springer Science and Business Media LLC