Systematic investigation of the prognostic impact of clonal status of somatic mutations across multiple cancer types
Systematic investigation of the prognostic impact of clonal status of somatic mutations across multiple cancer types
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DOI：
10.1016/j.ygeno.2022.110412
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发表时间：
2022-06-29
期刊：
影响因子：
4.4
通讯作者：
Xu，Jinyuan
中科院分区：
文献类型：
--
作者：
Cheng，Peng;Lan，Yujia;Xu，Jinyuan
肿瘤是遗传异质性的，许多突变实际上存在于亚克隆群体中。突变的克隆状态对准确的预后、临床处理有价值。本研究的目的是确定体细胞突变的克隆状态，并系统地评估其在各种癌症类型中的预后价值。我们共鉴定出227个克隆和432个亚克隆突变对预后有贡献，并证明克隆状态在改善突变相关临床指导中的重要性。我们进一步开发了一种定制的多步骤方法，以在泛癌症水平上识别克隆状态的基因特异性预后模式，并发现了一些癌症特异性预后模式。“亚克隆依赖性风险”亚模式是最常见的亚模式之一，它通常伴随着高度的基因组不稳定性和高度的肿瘤内异质性，可用于提高预后分析的准确性。我们的研究结果揭示了克隆状态，特别是亚克隆突变在临床生存中的重要性。
Tumors are genetically heterogeneous and many mutations are actually present in subclonal populations. The clonal status of mutations is valuable for accurate prognosis, clinical management. The aim of this study was to identify the clonal status of somatic mutations and systematically evaluate their prognostic values across various cancer types. We totally identified 227 clonal and 432 subclonal mutations contributed to prognosis and demonstrated the importance of clonal status in improving mutation-related clinical guidance. We further developed a customized multi-step approach to identify gene-specific prognostic patterns of clonal status at pan-cancer level and found some cancer-specific prognostic patterns. The ‘subclonal-dependent risk’ subpattern was one of the most common subpatterns, it usually accompanied by high genomic in-stability and high extent of intra-tumor heterogeneity and could be used to improve the accuracy of prognostic analysis. Our results revealed the importance of clonal status, especially subclonal mutation in clinical survival.