Abstract
Intratumour heterogeneity (ITH) and tumour evolution are well‐documented phenomena in human cancers. While the advent of next‐generation sequencing technologies has facilitated the large‐scale capture of genomic data, the field of single‐cell genomics is nascent but rapidly advancing and generating many new insights into the complex molecular mechanisms of tumour biology. In this review, we provide an overview of current single‐cell DNA sequencing technologies, exploring how recent methodological advancements have enumerated new insights into ITH and tumour evolution. Areas highlighted include the potential power of single‐cell genome sequencing studies to explore evolutionary dynamics contributing to tumourigenesis through to progression, metastasis, and therapy resistance. We also explore the use of in situ sequencing technologies to study ITH in a spatial context, as well as examining the use of single‐cell genomics to perform lineage tracing in both normal and malignant tissues. Finally, we consider the use of multimodal single‐cell sequencing technologies. Taken together, it is hoped that these many facets of single‐cell genome sequencing will improve our understanding of tumourigenesis, progression, and lethality in cancer, leading to the development of novel therapies. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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