癌症着丝粒的基因组景观。
The Genomic Landscape of Centromeres in Cancers.
机构信息
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, 48109, USA.
Program in Cancer Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
出版信息
Sci Rep. 2019 Aug 2;9(1):11259. doi: 10.1038/s41598-019-47757-6.
Centromere genomics remain poorly characterized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centromeric loci difficult to achieve. We here leverage a highly specific and targeted rapid PCR methodology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centromeric core and pericentromeric markers (α-satellite units and HERV-K copies) were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric endogenous retrovirus amplified by PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent a more comprehensive evaluation of centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression.
由于测序和生物信息学方法在技术上的限制，使得难以实现高分辨率的着丝粒定位，因此癌症中的着丝粒基因组学仍未得到充分描述。在这里，我们利用一种高度特异性和靶向性的快速 PCR 方法，定量评估癌细胞系和原代组织中的着丝粒基因组景观。与健康对照相比，基于 PCR 的着丝粒分析显示癌细胞和组织中的着丝粒和着丝粒周围序列存在广泛的异质性。与健康对照相比，在肿瘤样本中观察到着丝粒核心和着丝粒周围标记物（α-卫星单位和 HERV-K 拷贝）的定量减少。随后对通过 PCR 扩增的着丝粒周围内源性逆转录病毒进行系统发育分析表明，在恶性肿瘤环境中，许多着丝粒周围位点可能发生基因转换事件。我们的研究结果共同代表了在恶性肿瘤背景下对着丝粒遗传学的更全面评估，为了解着丝粒序列在癌症发生和发展中的进化和重排提供了有价值的见解。
Zotero 插件