Chromosomal Rearrangements and Altered Nuclear Organization: Recent Mechanistic Models in Cancer.
Chromosomal Rearrangements and Altered Nuclear Organization: Recent Mechanistic Models in Cancer.
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DOI：
10.3390/cancers13225860
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发表时间：
2021-11-22
期刊：
影响因子：
5.2
通讯作者：
Saccone S
中科院分区：
文献类型：
--
作者：
Federico C;Bruno F;Ragusa D;Clements CS;Brancato D;Henry MP;Bridger JM;Tosi S;Saccone S
在过去的几十年中开发的新方法和技术已经突出了基因组进入细胞核的精确空间组织，染色质结构在控制几种基因组功能中发挥着核心作用。基因在细胞分化过程中以明确的方式和明确的时间表达，基因组结构的改变可能导致遗传疾病，如癌症。在这里，我们回顾了基因组是如何在细胞核中组织的，以及基因组错误组织导致癌症疾病的证据。在过去的十年里，我们在了解基因组在间期核内的空间结构方面取得了重大进展。最近的分析证实了早期的分子细胞遗传学研究染色体定位间期核内，并提供了新的信息拓扑相关域（TADs）。检查基因组如何在间期核内组织的细微差别将为理解健康和疾病中的基因调控和表达提供基本信息。事实上，细胞核内单个基因位点的径向空间定位与特定基因的上调和下调有关，细胞核内正常基因组组织的破坏将导致细胞健康受损。在癌细胞中，核结构的重组可能发生在染色体重排（如易位、倒位或缺失）的情况下，基因重新定位可以改变它们的表达。到目前为止，很少有研究集中在径向基因定位和相关性的基因表达在癌症中。进一步的研究将提高我们对癌症的生物学机制的理解，特别是在白血病的发生和发展中，特别是在染色体重排的分子后果尚不清楚的情况下。在这篇综述中，我们总结了细胞核基因组组织领域的主要里程碑，以及可能导致癌症疾病的这种组织的改变。
New methodologies and technologies developed in the last few decades have highlighted the precise spatial organization of the genome into the cell nucleus, with chromatin architecture playing a central role in controlling several genome functions. Genes are expressed in a well-defined way and at a well-defined time during cell differentiation, and alterations in genome organization can lead to genetic diseases, such as cancers. Here we review how the genome is organized in the cell nucleus and the evidence of genome misorganization leading to cancer diseases. The last decade has seen significant progress in understanding how the genome is organized spatially within interphase nuclei. Recent analyses have confirmed earlier molecular cytogenetic studies on chromosome positioning within interphase nuclei and provided new information about the topologically associated domains (TADs). Examining the nuances of how genomes are organized within interphase nuclei will provide information fundamental to understanding gene regulation and expression in health and disease. Indeed, the radial spatial positioning of individual gene loci within nuclei has been associated with up- and down-regulation of specific genes, and disruption of normal genome organization within nuclei will result in compromised cellular health. In cancer cells, where reorganization of the nuclear architecture may occur in the presence of chromosomal rearrangements such as translocations, inversions, or deletions, gene repositioning can change their expression. To date, very few studies have focused on radial gene positioning and the correlation to gene expression in cancers. Further investigations would improve our understanding of the biological mechanisms at the basis of cancer and, in particular, in leukemia initiation and progression, especially in those cases where the molecular consequences of chromosomal rearrangements are still unclear. In this review, we summarize the main milestones in the field of genome organization in the nucleus and the alterations to this organization that can lead to cancer diseases.
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DOI：
10.1083/jcb.145.6.1119
发表时间：
1999-06-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Croft JA;Bridger JM;Boyle S;Perry P;Teague P;Bickmore WA
通讯作者：
Bickmore WA
影响因子：
1.6
作者：
DUTRILLAUX, B;COUTURIER, J;VIEGASPEQUIGNOT, E
通讯作者：
VIEGASPEQUIGNOT, E
影响因子：
3.5
作者：
D'Antoni, S;Mattina, T;Saccone, S
通讯作者：
Saccone, S
影响因子：
9.8
作者：
Branco MR;Pombo A
通讯作者：
Pombo A
影响因子：
3.7
作者：
Gandhi, Manoj S.;Stringer, James R.;Nikiforova, Marina N.;Medvedovic, Mario;Nikiforov, Yuri E.
通讯作者：
Nikiforov, Yuri E.