Higher order chromatin organization in cancer.
Higher order chromatin organization in cancer.
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DOI：
10.1016/j.semcancer.2012.12.001
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发表时间：
2013-04
影响因子：
14.5
通讯作者：
Feinberg AP
中科院分区：
文献类型：
--
作者：
Reddy KL;Feinberg AP
尽管我们对基因组如何在癌症中失调以及大量的分子诊断工具有了越来越多的了解，但癌症的前线和“金标准”检测仍然是病理学家对细胞和组织结构的总体变化的检测，最引人注目的是核解体。事实上，140 多年来人们就注意到癌症中的核形态经常被破坏。即使在今天，核形态测量也包括核大小、形状、DNA 含量（倍性）和“染色质组织”。鉴于核形状对癌症表型诊断的重要性，令人惊讶和沮丧的是，我们目前缺乏详细的了解来解释这些变化以及它们如何出现以及与细胞中的分子事件相关。这是一个隐含的假设，即染色质和表观遗传特征的扰动可能导致核结构的改变（反之亦然），并且这些扰动是癌症发生的核心。在这篇综述中，我们试图综合目前的研究成果，了解核纤层的染色质相互作用、表观遗传调节和基因调控如何在癌症中交叉，并提供关键实验的视角，这将有助于阐明核结构如何促成癌性表型。我们还讨论了对正常细胞核结构及其作为癌症诊断的历史认识。
In spite of our increased understanding of how genomes are dysregulated in cancer and a plethora of molecular diagnostic tools, the front line and ‘gold standard’ detection of cancer remains the pathologist’s detection of gross changes in cellular and tissue structure, most strikingly nuclear dis-organization. In fact, for over 140 years it has been noted that nuclear morphology is often disrupted in cancer. Even today, nuclear morphology measures include nuclear size, shape, DNA content (ploidy) and ‘chromatin organization’. Given the importance of nuclear shape to diagnoses of cancer phenotypes, it is surprising and frustrating that we currently lack a detailed understanding to explain these changes and how they might arise and relate to molecular events in the cell. It is an implicit hypothesis that perturbation of chromatin and epigenetic signatures may lead to alterations in nuclear structure (or vice versa) and that these perturbations lie at the heart of cancer genesis. In this review, we attempt to synthesize research leading to our current understanding on how chromatin interactions at the nuclear lamina, epigenetic modulation and gene regulation may intersect in cancer and offer a perspective on critical experiments that would help clarify how nuclear architecture may contribute to the cancerous phenotype. We also discuss the historical understanding of nuclear structure in normal cells and as a diagnostic in cancer.
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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：
8.4
作者：
Belt, E. J. Th.;Fijneman, R. J. A.;Meijer, G. A.
通讯作者：
Meijer, G. A.
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
2.9
作者：
Gilbert, Scott F.
通讯作者：
Gilbert, Scott F.
影响因子：
120.7
作者：
Bjornsson, Hans T.;Sigurdsson, Martin I.;Feinberg, Andrew P.
通讯作者：
Feinberg, Andrew P.