Tumor subclonal progression model for cancer hallmark acquisition
Tumor subclonal progression model for cancer hallmark acquisition
复制标题
用于获取癌症标志的肿瘤亚克隆进展模型
DOI：
10.1007/978-3-030-14160-8_12
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Shimamura T
中科院分区：
文献类型：
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作者：
Matsu Y;Miyano S;Shimamura T
癌症进化轨迹重建方法的最新进展为破译癌症生态系统中的亚克隆种群及其进化结构开辟了前景。癌症进化研究的一个重要挑战是如何将亚克隆中的遗传异常与亚克隆中的临床可解释和可操作的靶点联系起来。在这项研究中，我们的目标是开发一种新的方法，根据多区域测序数据获取癌症标志来构建肿瘤亚克隆进展模型。我们准备了一个亚克隆进化树，根据变异的等位基因频率推断，并从大规模的队列基因组数据中估计途径改变的概率。然后，我们构建了一棵途径改变的进化树，该树通过选择性分数来考虑途径改变的选择性。我们在一个肾透明细胞癌的数据集上展示了我们的方法的有效性。
Recent advances in the methods for reconstruction of cancer evolutionary trajectories opened up the prospects of deciphering the subclonal populations and their evolutionary architectures within cancer ecosystems. An important challenge of the cancer evolution studies is how to connect genetic aberrations in subclones to a clinically interpretable and actionable target in the subclones for individual patients. In this study, our aim is to develop a novel method for constructing a model of tumor subclonal progression in terms of cancer hallmark acquisition using multiregional sequencing data. We prepare a subclonal evolutionary tree inferred from variant allele frequencies and estimate pathway alteration probabilities from large-scale cohort genomic data. We then construct an evolutionary tree of pathway alterations that takes into account selectivity of pathway alterations via selectivity score. We show the effectiveness of our method on a dataset of clear cell renal cell carcinomas.