DNA甲基化在肺癌中的研究进展

表观遗传学主要是研究基因表达的变化,而这种变化能够通过减数分裂遗传,但不涉及有关基因碱基序列的改变.随着肿瘤发病机制研究在分子生物学方面的逐步深入,发现DNA甲基化、非编码RNA表达调控和组蛋白的修饰等表观遗传学(epigenetics)改变引起的调控机制异常与人体多种恶性肿瘤的发生发展过程有着密切联系.研究表明抑癌基因启动子区高度DNA甲基化状态在恶性肿瘤的发生发展和侵袭转移中发挥着重要作用.在肺癌发生的早期,出现很多DNA甲基化状态的改变.因此,甲基化检测可能对肺癌患者的早期诊断、治疗及预后评估具有重要意义.     

微小RNA与DNA甲基化相互调控在胃癌中的作用

表观遗传修饰在胃癌发生发展及预后中起重要作用.微小RNA( miRNA)和DNA甲基化是表观遗传学的两个重要调控机制.miRNA抑制靶基因信使RNA的翻译,参与基因转录后水平调控.基因启动子区CpG岛的异常甲基化与肿瘤的发生关系密切,可导致癌基因、抑癌基因或其他肿瘤相关基因的表达异常.胃癌中存在miRNA和DNA甲基化...     

DNA甲基转移酶在肿瘤发病机制中的研究进展北大核心CSCD

0引言 与经典的遗传学不同,表观遗传学是指在DNA序列未发生异常改变的前提下,基因的功能发生了叮遗传的信息变化,并最终导致了表型的改变。DNA甲基化是表观遗传学修饰的主要形式之一,而DNA甲基转移酶（DNA methyltransferase,DNMT）则是DNA甲基化的主要调节酶。本文就DNMT在肿瘤中的研究进展作一综述。     

淋巴瘤的表观遗传学及其临床意义

在肿瘤形成过程中包含两大类机制，即遗传学机制和表观遗传学机制。肿瘤的表观遗传学主要体现在DNA甲基化模式上，一些肿瘤抑制基因的启动子的高甲基化及整个基因组的低甲基化状态。对肿瘤表观遗传学深入研究将对淋巴瘤的发生发展机制和临床诊断治疗起到重要作用。     

淋巴瘤的表观遗传学及其临床意义

在肿瘤形成过程中包含两大类机制,即遗传学机制和表观遗传学机制。肿瘤的表观遗传学主要体现在DNA甲基化模式上,一些肿瘤抑制基因的启动子的高甲基化及整个基因组的低甲基化状态。对肿瘤表观遗传学深入研究将对淋巴瘤的发生发展机制和临床诊断治疗起到重要作用。     

骨肉瘤发生发展的分子生物学机制及相关治疗的研究进展

近年来，越来越多的实验和临床研究表明，骨肉瘤患者中存在众多潜在的分子靶点，但暂无针对相应靶点的治疗药物。骨肉瘤发生及发展相关的分子生物学改变，其主要机制包括：(1)DNA突变，(2)表观遗传学改变（非编码RNA调控、DNA甲基化、组蛋白修饰等）。全文讨论包含一系列可能成为骨肉瘤治疗潜在靶点的内在分子生物学改变，并对骨肉瘤发病机制进行分析，以期基于骨肉瘤的特异性分子改变而选择相关治疗策略，为骨肉瘤的治疗和研究提供新思路。     

DNA甲基化调控在免疫学研究中的进展

表观遗传学是研究基因序列不发生改变的情况下,基因表达发生了可以遗传的改变的一门学科。DNA甲基化是表观遗传学中进化上比较保守、相对比较稳定的一种表观修饰。DNA甲基化,特别是CpG岛的高甲基化,通常能够介导基因表达的稳定沉默。研究表明,DNA甲基化参与调控免疫系统的分化发育,DNA甲基化的异常也是包括肿瘤在内的众多免疫相关疾病发生、发展的关键致病因素。表观遗传学与免疫学的碰撞也为理解免疫学现象的分子调控机制提供了崭新的视角。本文将对近年来DNA甲基化调控在免疫学中的进展作一综述。     

DNA甲基化在肿瘤中的调控机制及其在肺癌中的研究进展

表观遗传修饰主要包括DNA甲基化、组蛋白修饰和染色质重塑等,DNA甲基化成为表观遗传学肿瘤研究的热点.DNA甲基化在基因的转录和转录后调控、miRNA基因表达调控和长链非编码RNA的转录后调控中发挥着关键作用,与肿瘤发生密切相关.DNA甲基化与miRNA在肿瘤中相互作用,两者之间存在反馈调节.PR结构域蛋白(PRDI-BF1 and RIZ ho-mology domain containing protein,PRDM)基因甲基化在肺癌中发挥重要作用,P16、RASSF1A、FHIT等基因甲基化与肺癌密切相关;EGFR甲基化、miRNA启动子区的甲基化,长链非编码RNAHOTAIR、TUG1等调控下游靶基因启动子区的甲基化均与肺癌密切相关.     

MicroRNA与DNA甲基化相互调节机制在肝细胞癌中的研究进展

肝细胞癌是原发性肝癌的主要类型,也是人类恶性程度较高的肿瘤之一,其发病机制至今尚未完全阐明.表观遗传学机制在肿瘤的发生、发展中起重要作用,DNA甲基化和微小RNA (microRNA,miRNA)的调控机制属于表观遗传学的研究范畴.研究表明,DNA甲基化及miRNA在肝细胞癌的形成中分别或协同发挥着重要作用,miRNA是一类在转录后水平调节基因表达的非编码短链RNA.研究表明,DNA甲基化和组蛋白修饰不仅可以调节蛋白编码基因的表达,而且可以调节miRNA的表达.在肝细胞癌中,一些异常表达的miRNAs(如miR-125b、miR-1-1、miR-124、miR-203和miR-191)是通过表观遗传学机制调控的.另外,在肝细胞癌中还发现了一类miRNAs通过调控表观遗传学通路中关键分子来改变整个基因组的表观遗传学状态.本文就DNA甲基化和miRNA之间复杂的相互调节机制在肝细胞癌发生和发展中的研究进展进行综述.     

DNA甲基化抑制剂在恶性淋巴瘤中的研究进展

DNA甲基化是生物基因表达调控的方式之一,其作为一种特殊的表观遗传事件在疾病的发生、发展中具有重要作用。近年来,随着基础医学研究的发展,研究人员在血液系统肿瘤尤其是恶性淋巴瘤中发现了基因的高甲基化,相关药物的研发及临床试验的开展也在不断推进。DNA甲基转移酶抑制剂（DNA methyltransferase inhibitors,DNMTIs）作为表观遗传药物通过抑制DNA甲基转移酶,干扰DNA转录的过程来发挥抗肿瘤作用,成为治疗肿瘤的新手段。目前,上市的DNMTI包括地西他滨和阿扎胞苷,其在血液系统恶性肿瘤和实体肿瘤的治疗中都取得了良好的疗效。本文主要针对DNA甲基化抑制剂在恶性淋巴瘤中的作用机制和临床研究的进展进行综述。      

MicroRNA epigenetic alterations in human cancer: one step forward in diagnosis and treatment

MicroRNAs (miRNAs) are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translational inhibition or messenger RNA (mRNA) degradation. Since the discovery of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding RNAs. By molecular cloning and bioinformatic approaches, miRNAs have been identified in viruses, plants and animals. miRNAs are predicted to negatively target up to one-third of human mRNAs. Cancer is a complex genetic disease caused by abnormalities in gene structure and expression. Previous studies have heavily focused on protein-coding genes; however, accumulating evidence is revealing an important role of miRNAs in cancer. Epigenetics is defined as mitotically and/or meiotically heritable changes in gene expression that are not accompanied by changes in DNA sequence. Given the critical roles of miRNAs and epigenetics in cancer, characterizing the epigenetic regulation of miRNAs will provide novel opportunities for the development of cancer biomarkers and/or the identification of new therapeutic targets in the foreseeable future.     

表观遗传学调控与妇科肿瘤发生、演进及治疗的研究进展

在卵巢肿瘤、子宫内膜癌以及宫颈癌中,已有许多研究证明了遗传学和表观遗传学修饰对肿瘤发生、发展的影响。以往研究证实癌基因、抑癌基因以及细胞信号传导通路异常导致肿瘤形成。与基因突变不同的是,表观遗传学并不是通过改变基因组序列,而是通过甲基化修饰、组蛋白修饰、ｍｉＲＮＡ调节等方式对基因组进行调控。甲基化异常、组蛋白修饰错误或ｍｉＲＮＡ调控紊乱与肿瘤细胞增殖、自噬、凋亡、细胞间粘附、浸润和转移密切相关。表观遗传学修饰作为肿瘤发生发展的关键因素,将其作为靶点应用于诊断治疗及评估预后将是重要的研究方向。     

DNA甲基化标志在胃肠肿瘤中的临床应用

DNA甲基化是高等真核生物中经常发生的现象,这种表观遗传学改变常发生在基因的启动子区域,并且不改变DNA序列和遗传密码,具有可逆性,在基因转录调控中发挥重要作用.已近知道抑癌基因和一些与正常细胞功能相关基因的转录失活与DNA甲基化有关,在胃肠肿瘤的发生,发展中起重要作用.随着对DNA甲基化的分子机制的进一步认识,以甲基化为基础的标志在临床的应用,尤其是肿瘤的防治,展现了广阔的前景.目前,这一标志及其相关技术在临床的应用涉及到诊断及治疗等方面,诸如患病风险评估、早期诊断、预后判定、复发监测、治疗反应监测和治疗计划的制定以及可作为治疗靶点等.就DNA甲基化肿瘤标志在胃肠肿瘤中的临床应用研究进展作一综述.     

B细胞淋巴瘤表观遗传学研究进展

表观遗传学是功能基因组学的重要组成部分,是研究DNA序列不发生变化但基因表达发生遗传性改变的一门遗传学分支学科,主要包括DNA甲基化、组蛋白修饰、染色体重塑和微小RNA(miRNA)等基因表达调节机制.表观遗传学调控机制在B细胞淋巴瘤的发展中具有重要作用,有研究表明在B细胞淋巴瘤中常见表观遗传学模式的不稳定性和分子突变.文章从DNA甲基化、组蛋白修饰、miRNA等方面对B细胞淋巴瘤的发生、发展、治疗及预后进行综述.     

Epigenetic Mechanisms and Events in Gastric Cancer-Emerging Novel Biomarkers

Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis. The DNA methylation is a chemical change in the DNA sequence that most commonly occurs at cytosine moiety of CpG dinucleotide and histone, primarily on N- terminal tail that ultimately effect the interaction of DNA with chromatin modifying protein.Hypermethylation of tumor suppressor genes and global hypomethylation of oncogenes are widely studied epigenetic modifications. There are large number of publish reports regarding epigenetic events involving gastric cancer. These changes are potentially useful in identifying markers for early diagnosis and management of this lethal malignancy. Also, role of specific miRNAs and long non coding RNAs in regulation of gene expression is gaining interest and is a matter of further investigation. In this review, we aimed to summarize major epigenetic events (DNA methylation) in gastric cancer along with alteration in miRNAs and long non coding RNAs which plays an important role in pathology of this poorly understood malignancy.     

Epigenetic changes in osteosarcoma

Osteosarcoma is one of the most prevalent primary bone tumors. The pathogenesis and molecular development of this tumor remains elusive. The prognosis is unfavorable due to lack of effective treatment methods. Recent advances in the epigenetics have brought a profound impact on the understanding of molecular mechanisms that lead to osteosarcoma. In this review, we summarized the current literature on epigenetic changes that are thought to contribute to the carcinogenesis of osteosarcoma, and discussed the potential diagnostic and therapeutic applications as well as future areas of research.     

Cancer epigenetics in clinical practice

Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence, epigenetic alterations contribute to the acquisition of hallmark tumor capabilities by regulating gene expression programs that promote tumorigenesis. Shifts in DNA methylation and histone mark patterns, the two main epigenetic modifications, orchestrate tumor progression and metastasis. These cancer-specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review summarizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation-based assays and epigenetic drugs already approved by the US Food and Drug Administration.     

Epigenetics in cancer: implications for early detection and prevention

Knowledge of the molecular events that occur during the early stages of cancer has advanced rapidly. The initiation and development of cancer involves several molecular changes, which include epigenetic alterations. Epigenetics is the study of modifications in gene expression that do not involve changes in DNA nucleotide sequences. Modifications in gene expression through methylation of DNA and remodelling of chromatin via histone proteins are believed to be the most important of the epigenetic changes. The study of epigenetics offers great potential for the identification of biomarkers that can be used to detect and diagnose cancer in its earliest stages and to accurately assess individual risk. There has been a recent surge of interest among researchers as variations in the methylation of DNA have been shown to be the most consistent molecular changes in many neoplasms. An important distinction between a genetic and an epigenetic change in cancer is that epigenetic changes can be reversed more easily by use of therapeutic interventions. The discovery of these basic premises should stimulate much future research on epigenetics.     

Mutational determinants of epigenetic instablity in myeloid malignancies

Until recently, myeloid neoplasms have been attributed to genomic and genetic instability leading to clonal outgrowth. However, it is now increasingly evident that epigenetic abnormalities also play a fundamental role in development of these malignancies. A growing body of evidence has underlined the involvement of epigenetic machinery in the malignant transformation of hematopoietic cells. Epigenetic dysfunction can lead to genetic alterations, including microsatellite instability, nucleotide changes, and chromosomal alterations. Conversely, putative epigenetic instability may be related to mutations of genes involved in epigenetic regulation. Therefore, this review focuses on epigenetic processes, including DNA methylation, post-translational histone modifications, and RNA interference via small noncoding RNAs, which play a critical role in controlling gene expression and are targets of dysregulation in many hematologic malignancies. Further, recent literature identified somatic mutations in several epigenetic regulators with a high frequency in myeloid malignancies.