The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates. We then integrated coordinates with genomic data to map exact spatial subclone locations, revealing how genetically distinct subclones grow and evolve spatially. We observed a phenotype of advanced and more aggressive subclonal growth in the tumour centre, characterized by an elevated burden of somatic copy number alterations and higher necrosis, proliferation rate and Fuhrman grade. Moreover, we found that metastasizing subclones preferentially originate from the tumour centre. Collectively, these observations suggest a model of accelerated evolution in the tumour interior, with harsh hypoxic environmental conditions leading to a greater opportunity for driver somatic copy number alterations to arise and expand due to selective advantage. Tumour subclone growth is predominantly spatially contiguous in nature. We found only two cases of subclone dispersal, one of which was associated with metastasis. The largest subclones spatially were dominated by driver somatic copy number alterations, suggesting that a large selective advantage can be conferred to subclones upon acquisition of these alterations. In conclusion, spatial dynamics is strongly associated with genomic alterations and plays an important role in tumour evolution.

实体瘤生长的遗传进化特征被越来越清楚地描述，但亚克隆生长的空间和物理性质仍不清楚。在这里，我们利用来自透明细胞肾细胞癌患者的 102 张宏观全肿瘤图像，以及来自 756 份活检的匹配遗传和表型数据。利用数字图像处理管道，肾脏病理学家标记了肿瘤和正常组织之间的边界，并将边界线和活检区域的位置提取到X和Y坐标。然后，我们将坐标与基因组数据整合以绘制精确的空间亚克隆位置，揭示遗传上不同的亚克隆如何在空间上生长和进化。我们在肿瘤中心观察到一种晚期和更具侵略性的亚克隆生长的表型，其特征是体细胞拷贝数改变的负担增加以及更高的坏死、增殖率和 Fuhrman 分级。此外，我们发现转移亚克隆优先起源于肿瘤中心。总的来说，这些观察结果表明了肿瘤内部加速进化的模型，在恶劣的缺氧环境条件下，由于选择性优势，驱动体细胞拷贝数改变出现和扩大的机会更大。肿瘤亚克隆生长本质上主要是空间连续的。我们只发现了两例亚克隆扩散，其中一例与转移有关。空间上最大的亚克隆以驱动体细胞拷贝数改变为主，这表明在获得这些改变后可以赋予亚克隆很大的选择优势。总之，空间动力学与基因组改变密切相关，并在肿瘤进化中发挥重要作用。