Breaking point: the genesis and impact of structural variation in tumours.
Breaking point: the genesis and impact of structural variation in tumours.
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DOI：
10.12688/f1000research.16079.1
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Semple, Colin
中科院分区：
文献类型：
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作者：
Ewing, Ailith;Semple, Colin
体细胞结构变异无疑在驱动肿瘤发生中起着重要作用。这是显而易见的，尽管在准确检测肿瘤中的结构变异及其断点方面仍然存在重大的技术挑战，尽管我们对结构变异对细胞功能的影响了解不完全。这些研究领域的发展有助于不断发现结构变异，对肿瘤的演变和对患者的临床重要性有明显的影响。最近的大型全基因组测序研究强化了我们的印象，即每个肿瘤都是突变的独特组合，但矛盾的是，我们也发现了肿瘤之间类似的单核苷酸和结构变异的全基因组模式。已经开发出统计方法来解卷积在样本中重复出现的突变模式或特征，从而提供有关在给定肿瘤中可能活跃的诱变剂和修复过程的信息。这些特征可以指导治疗，例如，通过突出特定肿瘤对特定化疗的脆弱性。因此，尽管肿瘤基因组的完整进化轨迹的完全重建目前仍然遥不可及，但有价值的数据已经出现，以改善癌症的治疗。
Somatic structural variants undoubtedly play important roles in driving tumourigenesis. This is evident despite the substantial technical challenges that remain in accurately detecting structural variants and their breakpoints in tumours and in spite of our incomplete understanding of the impact of structural variants on cellular function. Developments in these areas of research contribute to the ongoing discovery of structural variation with a clear impact on the evolution of the tumour and on the clinical importance to the patient. Recent large whole genome sequencing studies have reinforced our impression of each tumour as a unique combination of mutations but paradoxically have also discovered similar genome-wide patterns of single-nucleotide and structural variation between tumours. Statistical methods have been developed to deconvolute mutation patterns, or signatures, that recur across samples, providing information about the mutagens and repair processes that may be active in a given tumour. These signatures can guide treatment by, for example, highlighting vulnerabilities in a particular tumour to a particular chemotherapy. Thus, although the complete reconstruction of the full evolutionary trajectory of a tumour genome remains currently out of reach, valuable data are already emerging to improve the treatment of cancer.