兰州大学机构库 >学院待认领
DNA甲基化与血液肿瘤相关性研究
Alternative TitleThe Relationship between DNA methylation and Hematological Malignancies
张伟
Thesis Advisor张连生
2010-05-24
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
KeywordDNA甲基化 机制 诊断 治疗 检测方法
Abstract肿瘤表观遗传学是一门新兴的学科,主要包括DNA甲基化、组蛋白修饰、染色质修饰、基因组印记和非编码RNA调控等几个方面。其中,DNA甲基化与肿瘤的关系是研究的热点。基因DNA甲基化由DNA C5胞嘧啶甲基转移酶(DNA methyltransferase, Dnmt)催化,以S-腺苷甲硫氨酸(S-adenosylmethionine,SAM)为甲基供体,将甲基转移到胞嘧啶的第5位碳原子上。DNA甲基化的影响因素包括:DNA甲基转移酶、组蛋白甲基化、饮食等因素。DNA甲基化导致肿瘤的分子学机制有基因突变、DNA低甲基化对相关基因表达的影响、DNA 高甲基化对相关基因表达的影响、DNA甲基化转移酶表达增加对DNA甲基化的影响。DNA甲基化对血液疾病的诊断有着重要的临床价值,在许多情况下,甲基化的出现明显早于其恶性表型,而且肿瘤特异性与异常的DNA甲基化位点相关,特定基因甲基化可能是肿瘤早期检测分子指标之一。由于在恶性血液病中DNA高甲基化广泛存在,使恶性血液病的去甲基化治疗成为可能。DNA甲基化在大多数血液肿瘤中存在相同的癌基因和抑癌基因,也许发病的起始机制相同而表现为不同的血液疾病。随着对甲基化与肿瘤发展相关性研究的不断深入,人们逐渐认识到甲基化异常与传统的预后指标之间存在密切联系,主要包括4个方面:①甲基化异常与肿瘤分级、分期有明显的相关性;②DNA甲基化异常可促进肿瘤的侵袭和转移;③DNA特定基因的异常甲基化可作为肿瘤复发的独立预测因子;④甲基化影响患者的生存期。检测甲基化的改变有助于预后的判断,从而为临床上的风险评估和病情监测提供依据。基因启动子及其附近区域内CpG甲基化是导致众多基因沉默和基因印记的重要途径,通过测定启动子CpG岛甲基化状态了解基因是否沉默即去表达,为研究基因表达的情况提供了在DNA水平进行的重要监测途径,本文列举了一些DNA甲基化的检测手段。DNA异常甲基化是血液系统肿瘤发生的一个重要的分子机制,其中尤以抑癌基因的甲基化使其沉默最为重要,在细胞癌变过程中启动子异常甲基化是—个早期、频发事件,可作为肿瘤发生的敏感生物学指标,甲基化的进一步深入研究对临床有着十分重要的意义。
Other AbstractTumor epigenetics is a new subject, mainly including DNA methylation, histone modification and chromatin remodeling, genomic imprinting and the coding RNA control, etc. Among them, the DNA methylation and tumor relationship is the research focus. Gene DNA methylation of DNA C5 cytosine methyl shift enzyme (DNA methyltransferase, Dnmt) catalysis, Dnmt to S - adenosine state-of-art l-methionine (S - adenosylmethionine, SAM) for methyl donors, will methyl transferred to cytosine the fifth on carbon atoms. The influence factors of DNA methylation: DNA methylation transferase and histone methylation, diet, and other factors. DNA methylation tumours, including gene mutations of the pace of molecular mechanism of low, DNA methylation related gene expression, effects of DNA methylation on high the influence of gene expression and DNA methylation shift enzyme expression to increase the influence of DNA methylation. DNA methylation on blood disease diagnosis have important clinical value, in many cases, methylation earlier than the obvious malignant phenotype appear, and abnormal DNA methylation loci, specific genes with tumor-specific CpG island methylation is probably the most compelling tumor early detection of molecular indexes. Due to high in DNA methylation in malignant blood widespread make malignant blood to methylation, this paper treatment to be drugs to methylation reading. DNA methylation in most blood cancers exist the same cancer gene and tumor-suppressor genes, maybe onset starting mechanism for the same and the performance of different blood disease. Along with the development of methylation correlation with tumor the deepening of the research, there is a growing realization that methylation change and traditional between the prognostic indicators close contact. Mainly including four aspects: (1) the methylation change and staging, stages have obvious correlation. (2) the DNA methylation can promote abnormal invasion and metastasis of tumor. (3) methylation can be used as an independent predictor of tumor recurrence. (4) methylation affect survival. Detection methylation changes helped, and prognosis for clinical condition monitoring and risk assessment, provides the basis. Gene promoter and its nearby area CpG methylation is multiple genes realize to express (pause) and genetic signature important way, by means of measuring the CpG island promoter methylation state understand gene is to express, provides for the study o...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224165
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
张伟. DNA甲基化与血液肿瘤相关性研究[D]. 兰州. 兰州大学,2010.
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