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Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.
Cell ( IF 45.5 ) Pub Date : 2017-Nov-02 , DOI: 10.1016/j.cell.2017.10.014
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Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

中文翻译:

成人软组织肉瘤的全面综合基因组表征。

肉瘤是一个广泛的间叶恶性肿瘤家族,表现出显着的组织学多样性。我们描述了代表 6 种主要类型的 206 个成人软组织肉瘤的多平台分子景观。除了对个体肉瘤类型生物学的新见解外,我们还报告了三个总体发现:(1)与大多数上皮恶性肿瘤不同,这些肉瘤(滑膜肉瘤除外)的主要特征是拷贝数变化,突变负荷低,只有少数基因(TP53、ATRX、RB1)在肉瘤类型中高度反复突变;(2) 在肉瘤类型中,驱动通路的基因组和调节组多样性定义了与患者预后相关的分子亚型;(3) 从 DNA 甲基化和 mRNA 谱推断的免疫微环境,与结果相关,并可能为免疫检查点抑制剂的临床试验提供信息。总体而言,这项大规模分析揭示了以前未被发现的肉瘤类型特异性的拷贝数、甲基化、RNA 和蛋白质变化,为改进肉瘤治疗和与其他癌症类型的关系提供了见解。
更新日期:2017-11-02
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