Orr Jenny A, Hamilton Peter W
Department of Bioimaging and Informatics, Center for Cancer Research and Cell Biology, Queens University Belfast, Northern Ireland.
Anal Quant Cytol Histol. 2007 Feb;29(1):17-31.
Chromatin phenotype is known to be significantly disrupted in cancer. This has been demonstrated in many morphologic studies on cancer and in recent years by the application of digital texture analysis for quantitative evaluation of chromatin phenotype in neoplasia. Studies have consistently demonstrated the role of chromatin phenotype as a biomarker of diagnosis and prognosis. The underlying molecular mechanisms for chromatin reorganization and its role as a biomarker are largely unknown, but epigenetic processes are likely to be a main factor that not only modify chromatin arrangement but in doing so alter gene expression profiles in a reversible fashion. Of the range of epigenetic modifications that might control chromatin phenotype, histone acetylation is a strong candidate because of its role in the direct modification of chromatin, both through local relaxation of nucleosomal structure and recruitment of chromatin remodeling complexes. The reversible nature of histone acetylation is therapeutically attractive for treatment of aberrant histone acetylation; however, it still remains to be seen whether histone deacetylase inhibitors are clinically applicable or for use primarily as valuable research tools. This review explores the role of histone acetylation in cancer development, as a potential therapeutic candidate and a potential biomarker in tissue pathology.
已知染色质表型在癌症中会受到显著破坏。这在许多关于癌症的形态学研究中得到了证实，近年来通过应用数字纹理分析对肿瘤形成中的染色质表型进行定量评估也得到了证实。研究一致证明染色质表型作为诊断和预后生物标志物的作用。染色质重组的潜在分子机制及其作为生物标志物的作用在很大程度上尚不清楚，但表观遗传过程可能是一个主要因素，它不仅会改变染色质排列，而且会以可逆方式改变基因表达谱。在可能控制染色质表型的一系列表观遗传修饰中，组蛋白乙酰化是一个有力的候选者，因为它通过核小体结构的局部松弛和染色质重塑复合物的募集，在染色质的直接修饰中发挥作用。组蛋白乙酰化的可逆性在治疗异常组蛋白乙酰化方面具有治疗吸引力；然而，组蛋白脱乙酰酶抑制剂是否适用于临床或主要用作有价值的研究工具仍有待观察。本综述探讨了组蛋白乙酰化在癌症发展中的作用，作为组织病理学中的潜在治疗候选物和潜在生物标志物。
