Epigenetic regulation of gene expression in cancer: techniques, resources and analysis.
Epigenetic regulation of gene expression in cancer: techniques, resources and analysis.
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DOI：
10.1093/bfgp/elx018
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Fertig EJ
中科院分区：
文献类型：
--
作者：
Kagohara LT;Stein-O'Brien GL;Kelley D;Flam E;Wick HC;Danilova LV;Easwaran H;Favorov AV;Qian J;Gaykalova DA;Fertig EJ
癌症是一种复杂的疾病，甚至在单个恶性细胞中，由许多信号通路的异常活动驱动。表观遗传变化是这些功能变化的关键介质，这些功能变化驱动和维持恶性表型。DNA甲基化、组蛋白乙酰化和甲基化、非编码RNA、翻译后修饰的变化都是癌症的表观遗传驱动因素，与DNA序列的变化无关。这些表观遗传学改变曾经被认为仅对恶性表型维持至关重要。现在，表观遗传改变也被认为是破坏保护细胞免受不受控制的生长、更长的存活和在远离原始组织的部位建立的重要途径的关键。在这篇综述中，我们主要关注癌症中的DNA甲基化和染色质结构。这些改变的确切功能作用是使用新兴的高通量方法和生物信息学分析工具进行积极研究的领域。因此，本文还介绍了这些高通量的测量技术，公共领域的数据库的高通量表观遗传学数据在肿瘤和模型系统和生物信息学算法进行分析。将这些表观遗传学数据与基因组学数据联合收割机相结合的生物信息学数据的进展对于推断癌症中特定表观遗传学改变的功能至关重要。这些综合算法也是本文的重点。使用这些新兴技术的未来研究将阐明癌症表观基因组的改变如何在肿瘤发生和发展期间与遗传畸变合作。这种更深入的理解对于未来使用表观遗传学生物标志物和使用新兴表观遗传疗法的精准医学的研究至关重要。
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways in even individual malignant cells. Epigenetic changes are critical mediators of these functional changes that drive and maintain the malignant phenotype. Changes in DNA methylation, histone acetylation and methylation, noncoding RNAs, posttranslational modifications are all epigenetic drivers in cancer, independent of changes in the DNA sequence. These epigenetic alterations were once thought to be crucial only for the malignant phenotype maintenance. Now, epigenetic alterations are also recognized as critical for disrupting essential pathways that protect the cells from uncontrolled growth, longer survival and establishment in distant sites from the original tissue. In this review, we focus on DNA methylation and chromatin structure in cancer. The precise functional role of these alterations is an area of active research using emerging high-throughput approaches and bioinformatics analysis tools. Therefore, this review also describes these high-throughput measurement technologies, public domain databases for high-throughput epigenetic data in tumors and model systems and bioinformatics algorithms for their analysis. Advances in bioinformatics data that combine these epigenetic data with genomics data are essential to infer the function of specific epigenetic alterations in cancer. These integrative algorithms are also a focus of this review. Future studies using these emerging technologies will elucidate how alterations in the cancer epigenome cooperate with genetic aberrations during tumor initiation and progression. This deeper understanding is essential to future studies with epigenetics biomarkers and precision medicine using emerging epigenetic therapies.
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影响因子：
19
作者：
Böhmdorfer G;Wierzbicki AT
通讯作者：
Wierzbicki AT
影响因子：
5.6
作者：
Barutcu AR;Fritz AJ;Zaidi SK;van Wijnen AJ;Lian JB;Stein JL;Nickerson JA;Imbalzano AN;Stein GS
通讯作者：
Stein GS
影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
影响因子：
3.5
作者：
Baylin, SB;Esteller, M;Herman, JG
通讯作者：
Herman, JG
影响因子：
14.9
作者：
Adorján, P;Distler, J;Olek, A
通讯作者：
Olek, A