Principles of Reconstructing the Subclonal Architecture of Cancers
Principles of Reconstructing the Subclonal Architecture of Cancers
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DOI：
10.1101/cshperspect.a026625
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发表时间：
2017-08-01
影响因子：
5.4
通讯作者：
Van Loo, Peter
中科院分区：
文献类型：
--
作者：
Dentro, Stefan C.;Wedge, David C.;Van Loo, Peter
大多数癌症从单个创始细胞通过一系列由体细胞突变驱动的克隆扩增进化而来。这些克隆扩增可以导致几个共存的亚克隆共享突变的子集。大规模平行测序数据的分析可以通过鉴定具有共享突变的细胞群体来推断肿瘤的亚克隆组成。我们描述的原则，通过单核苷酸变异（SNV）或拷贝数改变（CNA）从批量或单细胞测序亚克隆重建。这些原理包括估计SNV和CNA的肿瘤细胞分数，从单样本和多样本病例中进行SNV聚类，以及单细胞测序。亚克隆重建方法的应用提供了对肿瘤进化的关键见解，识别亚克隆驱动突变，平行进化模式和细胞群体之间突变特征的差异，并表征治疗抗性，扩散和转移的机制。
Most cancers evolve from a single founder cell through a series of clonal expansions that are driven by somatic mutations. These clonal expansions can lead to several coexisting subclones sharing subsets of mutations. Analysis of massively parallel sequencing data can infer a tumor's subclonal composition through the identification of populations of cells with shared mutations. We describe the principles that underlie subclonal reconstruction through single nucleotide variants (SNVs) or copy number alterations (CNAs) from bulk or single-cell sequencing. These principles include estimating the fraction of tumor cells for SNVs and CNAs, performing clustering of SNVs from single-and multisample cases, and single-cell sequencing. The application of subclonal reconstruction methods is providing key insights into tumor evolution, identifying subclonal driver mutations, patterns of parallel evolution and differences in mutational signatures between cellular populations, and characterizing the mechanisms of therapy resistance, spread, and metastasis.