MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
J Pathol. 2022 Jul;257(4):479-493. doi: 10.1002/path.5901. Epub 2022 Apr 28.
Structural variants (SVs) represent a major source of aberration in tumour genomes. Given the diversity in the size and type of SVs present in tumours, the accurate detection and interpretation of SVs in tumours is challenging. New classes of complex structural events in tumours are discovered frequently, and the definitions of the genomic consequences of complex events are constantly being refined. Detailed analyses of short-read whole-genome sequencing (WGS) data from large tumour cohorts facilitate the interrogation of SVs at orders of magnitude greater scale and depth. However, the inherent technical limitations of short-read WGS prevent us from accurately detecting and investigating the impact of all the SVs present in tumours. The expanded use of long-read WGS will be critical for improving the accuracy of SV detection, and in fully resolving complex SV events, both of which are crucial for determining the impact of SVs on tumour progression and clinical outcome. Despite the present limitations, we demonstrate that SVs play an important role in tumourigenesis. In particular, SVs contribute significantly to late-stage tumour development and to intratumoural heterogeneity. The evolutionary trajectories of SVs represent a window into the clonal dynamics in tumours, a comprehensive understanding of which will be vital for influencing patient outcomes in the future. Recent findings have highlighted many clinical applications of SVs in cancer, from early detection to biomarkers for treatment response and prognosis. As the methods to detect and interpret SVs improve, elucidating the full breadth of the complex SV landscape and determining how these events modulate tumour evolution will improve our understanding of cancer biology and our ability to capitalise on the utility of SVs in the clinical management of cancer patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
结构变异（SV）是肿瘤基因组中变异的主要来源。鉴于肿瘤中存在的 SV 大小和类型的多样性，准确检测和解释肿瘤中的 SV 具有挑战性。肿瘤中经常发现新的复杂结构事件类别，并且复杂事件的基因组后果的定义也在不断完善。对来自大型肿瘤队列的短读全基因组测序（WGS）数据进行详细分析，有助于在更大规模和更深层次上检测 SV。然而，短读 WGS 的固有技术限制阻止我们准确检测和研究肿瘤中所有 SV 的影响。广泛使用长读 WGS 将是提高 SV 检测准确性和全面解析复杂 SV 事件的关键，这两者对于确定 SV 对肿瘤进展和临床结局的影响都至关重要。尽管存在目前的局限性，但我们证明 SV 在肿瘤发生中起着重要作用。特别是，SV 对晚期肿瘤发展和肿瘤内异质性有重大贡献。SV 的进化轨迹代表了肿瘤克隆动力学的一个窗口，全面了解这一点对于未来影响患者结局至关重要。最近的发现强调了 SV 在癌症中的许多临床应用，从早期检测到治疗反应和预后的生物标志物。随着检测和解释 SV 的方法的改进，阐明复杂 SV 景观的全貌，并确定这些事件如何调节肿瘤进化，将提高我们对癌症生物学的理解，并提高我们利用 SV 在癌症患者临床管理中的能力。© 2022 作者。The Journal of Pathology 由 John Wiley & Sons Ltd 代表英国和爱尔兰的病理学学会出版。
