Integrated exome and RNA sequencing of dedifferentiated liposarcoma
Integrated exome and RNA sequencing of dedifferentiated liposarcoma
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DOI：
10.1038/s41467-019-13286-z
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发表时间：
2019-12-12
影响因子：
16.6
通讯作者：
Matsuda, Koichi
中科院分区：
文献类型：
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作者：
Hirata, Makoto;Asano, Naofumi;Matsuda, Koichi
与临床特征相关的去分化脂肪肉瘤（DDLPS）的基因组特征仍有待确定。在这里，我们在115个DDLPS肿瘤中进行了整合的全外显子组和RNA测序分析，并对8个DDLPS样本的分化良好和去分化成分进行了比较基因组分析。一些体细胞拷贝数改变（SCNA），包括12 q15的增加，被确定为常见的基因组改变。CTDSP 1/2-DNM 3 OS融合基因在DDLPS肿瘤的子集中被鉴定。基于SCNA与临床特征的关联，DDLPS肿瘤被聚类为三组。这种聚类可以独立地预测临床结果。高分化和去分化组分之间的比较分析确定了两类基因组改变：与肿瘤发生相关的共享改变和与恶性转化相关的去分化特异性改变。这种大规模的基因组分析揭示了DDLPS的发展和进展的机制，并提供了可能有助于DDLPS管理的改进的见解。
The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.