Non-coding genetic variation in cancer.
Non-coding genetic variation in cancer.
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DOI：
10.1016/j.coisb.2016.12.017
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发表时间：
2017-03
影响因子：
3.7
通讯作者：
Khurana E
中科院分区：
文献类型：
--
作者：
Cuykendall TN;Rubin MA;Khurana E
癌症基因组中的绝大多数体细胞变异发生在非编码区。然而，在过去的十年中，癌症基因组学的进展主要集中在编码区，这在很大程度上是由于全基因组测序(WGS)的高昂成本。最近的技术进步降低了测序成本，导致目前获得了数千个肿瘤全基因组序列，这导致了对非编码驱动因素的追逐。最具特征的调控驱动因素是TERT启动子，并已在许多癌症类型中发现。尽管发生在非编码区的体细胞变异的比例较大，但到目前为止识别的非编码驱动程序的数量远远少于编码区驱动程序的数量。在这里，我们讨论可能会阻碍检测非编码驱动程序的原因。我们还检查了肿瘤细胞中非编码遗传变异和表观遗传状态之间的关系，并断言需要额外的表观遗传学数据集作为理解癌症调控网络重新布线的先决条件。
The vast majority of somatic variants in cancer genomes occur in non-coding regions. However, progress in cancer genomics in the past decade has been mostly focused on coding regions, largely due to the prohibitive cost of whole genome sequencing (WGS). Recent technological advances have decreased sequencing costs leading to the current acquisition of thousands of tumor whole genome sequences which has led to a hunt for non-coding drivers. The most well characterized regulatory drivers are in the TERT promoter and have been identified in many cancer types. Despite the larger fraction of somatic variants occurring in non-coding regions, the number of non-coding drivers identified so far is much less than the number of coding region drivers. Here we discuss reasons that may hinder the detection of non-coding drivers. We also examine the relationship between non-coding genetic variation and epigenetic state in tumor cells and assert the need for additional epigenetic data sets as a prerequisite for understanding the rewiring of regulatory networks in cancer.