Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer¹. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics² to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.

确定从良性组织到恶性组织的转变是改进癌症早期诊断的基础¹。在这里，我们使用系统方法原位研究空间基因组完整性并描述以前未识别的克隆关系。我们使用了空间分辨的转录组学²推断良性和恶性组织中跨多个器官的 >120,000 个区域的空间拷贝数变化。我们证明，使用针对前列腺的全器官方法，全基因组拷贝数变异揭示了肿瘤内和附近良性组织中的不同克隆模式。我们的结果提出了一个模型，说明基因组不稳定性如何在组织学良性组织中出现，这可能代表癌症进化的早期事件。我们强调在组织环境中捕捉分子和空间连续体的力量，并挑战治疗范式（包括局部治疗）的基本原理。