Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.
Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.
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DOI：
10.1038/s41559-021-01586-x
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发表时间：
2022-01
影响因子：
16.8
通讯作者：
Bates PA
中科院分区：
文献类型：
--
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
遗传肿瘤内异质性燃料克隆进化，但我们对临床相关的克隆动力学的理解仍然有限。我们通过建模和真实的肿瘤分析相结合，研究了肾透明细胞癌克隆多样化的空间和时间特征。我们观察到，肿瘤生长的模式，表面或体积，影响亚克隆多样化的程度，使患者肿瘤的克隆多样性的解释。增殖和坏死的特定模式解释了肿瘤中的克隆扩张和平行进化和微多样性的出现。在硅片时间过程的研究揭示了可检测的亚克隆多样化之前的萌芽结构的外观。有趣的是，我们观察到早期肾透明细胞癌中出芽结构的放射学证据，表明未来的克隆演变可能是可预测的。我们的研究结果提供了一个窗口，临床相关的克隆进化的时间和空间特征。使用联合建模和肿瘤分析方法研究TRACERx肾脏研究中亚克隆演变的时间和空间模式。研究早期肿瘤的肿瘤形状和克隆多样性的空间特征可以预测肿瘤的进展和亚克隆多样化的模式。
Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution. A combined modelling and tumour analysis approach is used to study the temporal and spatial patterns of subclone evolution in the TRACERx renal study. Studying the tumour shape and spatial features of clonal diversity in early-stage tumours may allow the prediction of tumour progression and patterns of subclone diversification over time.
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影响因子：
64.8
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