急性髓系白血病(acute myeloid leukaemia,AML)是一组造血细胞异常增殖和分化抑制造成的恶性克隆性血液疾病,具有明显异质性,有单个或多个分子遗传学事件参与其发病[1]。世界卫生组织(World Health Organization,WHO)根据白血病患者临...急性髓系白血病(acute myeloid leukaemia,AML)是一组造血细胞异常增殖和分化抑制造成的恶性克隆性血液疾病,具有明显异质性,有单个或多个分子遗传学事件参与其发病[1]。世界卫生组织(World Health Organization,WHO)根据白血病患者临床特点及形态学(morphology,M)、细胞免疫学(immunology,I)、细胞遗传学(cytogenetic,C)、分子生物学(molecular biology,M)异常制定了MICM分型,指导临床对白血病的诊断分型、个体治疗和预后判断。随着现今医学的发展及患者的期望值升高,对白血病的治疗方案愈来愈趋向于个体化、精准化、靶向化。DNA甲基化作为AML表观遗传学调控的常见模式,对其研究促进了近年来DNA甲基化治疗药物的发展,给AML的靶向治疗提供更多选择。展开更多
OBJECTIVE This study is to investigate the prevalence ofpromoter CpG island methylation of O^6-methylguananine-DNAmethyltransferase (MGMT), mismatch repair genes (hMLH1 andhMSH2) in both tumor and serum samples of gli...OBJECTIVE This study is to investigate the prevalence ofpromoter CpG island methylation of O^6-methylguananine-DNAmethyltransferase (MGMT), mismatch repair genes (hMLH1 andhMSH2) in both tumor and serum samples of gliomas.METHODS Methylation-specific PCR (MSP) was employed todetect promoter CpG island methylation of the MGMT, hMLH1and hMSH2 genes in 39 samples taken from surgery and 32samples of pretreatment serum all from the patients with gliomas.RESULTS Promoter CpG island methylation of MGMT, hMLH1and hMSH2 was detected and the results were 46.2%, 10.3% and20.5%, respectively in tumor DNA of the cases with gliomas,and 40.6%, 9.4% and 18.8%, respectively in serum DNA of thecases. The methylation pattern in primary tumor and serum wasfound to be concordant in matched tissue and serum samplesof 21 patients. In the cases with positive result of methylationfor MGMT, hMLH1 and hMSH2 in tumor tissues, the results ofdetection for those in the paired serum sample were 77.8% (7/9),66.7% (2/3) and 75.0 % (3/4), respectively. False positive resultswere not obtained in any of the patients who did not exhibitmethylation. No association was found between the promotermethylation of MGMT, hMLH1, and hMSH2 genes in primarygliomas and gender, age, localization, grade of malignant or tumorstage.CONCLUSION Promoter CpG island methylation is a frequentevent in gliomagenesis. Methylation analysis appears to bea promising predictive factor of the prognosis for the gliomapatients treated with alkylating drugs and a noninvasive tumormarker in serum DNA.展开更多
基金supported by a grant from National Natural Science Foundation of China(No.30671995).
文摘OBJECTIVE This study is to investigate the prevalence ofpromoter CpG island methylation of O^6-methylguananine-DNAmethyltransferase (MGMT), mismatch repair genes (hMLH1 andhMSH2) in both tumor and serum samples of gliomas.METHODS Methylation-specific PCR (MSP) was employed todetect promoter CpG island methylation of the MGMT, hMLH1and hMSH2 genes in 39 samples taken from surgery and 32samples of pretreatment serum all from the patients with gliomas.RESULTS Promoter CpG island methylation of MGMT, hMLH1and hMSH2 was detected and the results were 46.2%, 10.3% and20.5%, respectively in tumor DNA of the cases with gliomas,and 40.6%, 9.4% and 18.8%, respectively in serum DNA of thecases. The methylation pattern in primary tumor and serum wasfound to be concordant in matched tissue and serum samplesof 21 patients. In the cases with positive result of methylationfor MGMT, hMLH1 and hMSH2 in tumor tissues, the results ofdetection for those in the paired serum sample were 77.8% (7/9),66.7% (2/3) and 75.0 % (3/4), respectively. False positive resultswere not obtained in any of the patients who did not exhibitmethylation. No association was found between the promotermethylation of MGMT, hMLH1, and hMSH2 genes in primarygliomas and gender, age, localization, grade of malignant or tumorstage.CONCLUSION Promoter CpG island methylation is a frequentevent in gliomagenesis. Methylation analysis appears to bea promising predictive factor of the prognosis for the gliomapatients treated with alkylating drugs and a noninvasive tumormarker in serum DNA.
