Unravelling the tumour genome: The evolutionary and clinical impacts of structural variants in tumourigenesis.
Unravelling the tumour genome: The evolutionary and clinical impacts of structural variants in tumourigenesis.
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解开肿瘤基因组：结构变异在肿瘤发生中的进化和临床影响。
DOI：
10.1002/path.5901
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发表时间：
2022-07
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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结构变异体（SV）是肿瘤基因组畸变的主要来源。鉴于肿瘤中存在的SV的大小和类型的多样性，准确检测和解释肿瘤中的SV是具有挑战性的。肿瘤中复杂结构事件的新类别经常被发现，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）数据的详细分析有助于以更大的规模和深度询问SV。然而，短读WGS固有的技术局限性使我们无法准确检测和研究肿瘤中存在的所有SV的影响。长读WGS的扩展使用对于提高SV检测的准确性和完全解决复杂SV事件至关重要，这两者对于确定SV对肿瘤进展和临床结局的影响至关重要。尽管目前的局限性，我们证明，SV在肿瘤发生中发挥着重要作用。特别是，SV对晚期肿瘤发展和肿瘤内异质性有显著影响。SV的进化轨迹代表了肿瘤中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预后至关重要。最近的研究结果突出了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景观的全部广度并确定这些事件如何调节肿瘤演变将提高我们对癌症生物学的理解以及我们利用SV在癌症患者临床管理中的效用的能力。版权所有© 2022作者。病理学杂志由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版。
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.
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影响因子：
30.8
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Bielski CM;Taylor BS
通讯作者：
Taylor BS
DOI：
10.1038/nrg.2015.25
发表时间：
2016-04
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Carvalho CM;Lupski JR
通讯作者：
Lupski JR
影响因子：
30.8
作者：
Akdemir, Kadir C.;Le, Victoria T.;Zhang, Cheng-Zhong
通讯作者：
Zhang, Cheng-Zhong