Mutation divergence over space in tumour expansion.
Mutation divergence over space in tumour expansion.
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DOI：
10.1098/rsif.2023.0542
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发表时间：
2023-11
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影响因子：
--
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肿瘤演变中的突变积累是肿瘤内异质性（ITH）的一个主要原因，这通常会导致治疗期间的耐药性。以前的多区域测序研究表明，患者体内样本之间的突变差异很常见，空间采样对于获得肿瘤测量的完整图像非常重要。然而，突变异质性与肿瘤扩展模式，采样距离以及采样方法之间的关系的定量比较仍然很少。在这里，我们研究突变如何通过改变采样距离和肿瘤扩张模式，使用基于个人的模拟在空间上发散。我们测量ITH的Jaccard指数之间的样本和量化ITH如何增加采样距离，其模式在各种采样方法和大小。我们还比较了不同肿瘤扩张模式和样本量下基于变异等位基因频率分布的推断突变率。在指数快速扩张的肿瘤中，突变率总是可以针对任何采样大小来推断。然而，与真实值相比的准确度随着采样大小的减小而降低，其中小的采样大小导致突变率的高估计。此外，当肿瘤扩张缓慢时，例如在表面生长中，这种推断变得不可靠。
Mutation accumulation in tumour evolution is one major cause of intra-tumour heterogeneity (ITH), which often leads to drug resistance during treatment. Previous studies with multi-region sequencing have shown that mutation divergence among samples within the patient is common, and the importance of spatial sampling to obtain a complete picture in tumour measurements. However, quantitative comparisons of the relationship between mutation heterogeneity and tumour expansion modes, sampling distances as well as the sampling methods are still few. Here, we investigate how mutations diverge over space by varying the sampling distance and tumour expansion modes using individual-based simulations. We measure ITH by the Jaccard index between samples and quantify how ITH increases with sampling distance, the pattern of which holds in various sampling methods and sizes. We also compare the inferred mutation rates based on the distributions of variant allele frequencies under different tumour expansion modes and sampling sizes. In exponentially fast expanding tumours, a mutation rate can always be inferred for any sampling size. However, the accuracy compared with the true value decreases when the sampling size decreases, where small sampling sizes result in a high estimate of the mutation rate. In addition, such an inference becomes unreliable when the tumour expansion is slow, such as in surface growth.
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影响因子：
16.8
作者：
Fu X;Zhao Y;Lopez JI;Rowan A;Au L;Fendler A;Hazell S;Xu H;Horswell S;Shepherd STC;Spencer CE;Spain L;Byrne F;Stamp G;O'Brien T;Nicol D;Augustine M;Chandra A;Rudman S;Toncheva A;Furness AJS;Pickering L;Kumar S;Koh DM;Messiou C;Dafydd DA;Orton MR;Doran SJ;Larkin J;Swanton C;Sahai E;Litchfield K;Turajlic S;TRACERx Renal Consortium;Bates PA
通讯作者：
Bates PA
影响因子：
3.5
作者：
Tomasetti, Cristian
通讯作者：
Tomasetti, Cristian
DOI：
10.1073/pnas.2006487119
发表时间：
2022-08-30
影响因子：
11.1
作者：
Schencka, Ryan O.;Kim, Eunjung;Bravo, Rafael R.;West, Jeffrey;Leedham, Simon;Shibata, Darryl;Anderson, Alexander R. A.
通讯作者：
Anderson, Alexander R. A.
对抗癌疗法的耐药性的进化。
影响因子：
2
作者：
Foo, Jasmine;Michor, Franziska
通讯作者：
Michor, Franziska
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.