Identification of neutral tumor evolution across cancer types.
Identification of neutral tumor evolution across cancer types.
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DOI：
10.1038/ng.3489
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发表时间：
2016-03
期刊：
影响因子：
30.8
通讯作者：
Sottoriva A
中科院分区：
文献类型：
--
作者：
Williams MJ;Werner B;Barnes CP;Graham TA;Sottoriva A
尽管对癌症基因组进行了非凡的努力，但根据癌症演变解释大量基因组数据仍然具有挑战性。在这里，我们表明，中性肿瘤的演变结果在幂律分布的突变等位基因的频率报告的下一代测序肿瘤散装样品。我们发现，中性幂律符合高精度323 904癌症从14种类型，从不同的队列中选择。在被鉴定为中性的恶性肿瘤中，所有克隆选择都发生在癌症生长开始之前，而不是在后来出现的亚克隆中，导致许多乘客突变，这些突变是肿瘤内异质性的原因。在中性框架内重新分析癌症测序数据允许测量每个患者的体内突变率以及突变的顺序和时间。这一结果提供了一种新的方法来解释现有的癌症基因组数据，并区分功能性和非功能性肿瘤内异质性。
Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power-law fits with high precision 323 of 904 cancers from 14 types, selected from different cohorts. In malignancies identified as neutral, all clonal selection occurred prior to the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intra-tumor heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intra-tumor heterogeneity.