AIM:To investigate aberrant DNA methylation of CpG islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma...AIM:To investigate aberrant DNA methylation of CpG islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma(tu-bular or villous/tubulovillous)patients,and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1(hMLH1),Cyclin-dependent kinase inhibitor 2A(CDKN2A/p16),and O-6-methylguanine DNA methyltransferase(MGMT),as well as their rela- tion to MSI. RESULTS:The frequency of promoter methylation for each locus increased in the sequence healthy tissue/adenoma/carcinoma.MGMT showed the highest frequency in each group.MGMT and CDKN2A/p16 presented a statistically significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas(tubular vs tubullovillous and villous adenomas).All patients with tubulovillous/villous adenomas,as well as all colorectal cancer patients,showed promoter methylation in at least one of the examined loci.These findings suggest a potentially crucial role for methylation in the polyp/adenoma to cancer progres- sion in colorectal carcinogenesis.MSI and methylation seem to be interdependent,as simultaneous hMLH1, CDKN2A/p16,and MGMT promoter methylation was present in 8/9 colorectal cancer patients showing the MSI phenotype. CONCLUSION:Methylation analysis of hMLH1,CD- KN2A/p16,and MGMT revealed specific methylation profiles for tubular adenomas,tubulovillous/villous adenomas,and colorectal cancers,supporting the use of these alterations in assessment of colorectal tumorigenesis.展开更多
Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recen...Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.展开更多
脂联素(Adiponectin)是至今发现的唯一与肥胖呈负相关的脂肪细胞特异性蛋白,是调控生物体的能量稳态、葡萄糖代谢和脂肪代谢的脂源性细胞因子之一。生物信息学分析发现,adiponectin基因启动子区-1500～-1350bp是CpG位点的富集区域。为...脂联素(Adiponectin)是至今发现的唯一与肥胖呈负相关的脂肪细胞特异性蛋白,是调控生物体的能量稳态、葡萄糖代谢和脂肪代谢的脂源性细胞因子之一。生物信息学分析发现,adiponectin基因启动子区-1500～-1350bp是CpG位点的富集区域。为了进一步研究脂联素基因的表达调控研究,文章从表观遗传学角度出发,通过Real-time PCR与甲基化特异性PCR(Methylation special PCR,MSP)的方法对脂联素基因的表达及其启动子区的甲基化状况进行了分析。结果表明,在adiponectin基因启动子区CG富集的区域(-1500～-1350bp)中,90日龄长白猪大多去甲基化(83%),90日龄蓝塘猪部分去甲基化(33%),成年蓝塘猪全是高度甲基化(100%),成年长白猪部分去甲基化(33%)。甲基化与去甲基化过程主要发生在某些特定CpG位点。脂联素基因在猪肌肉组织中以高度甲基化状态为主,这一结果与该基因在肌肉组织中表达量相吻合。以上结果提示,随个体发育,脂联素基因的甲基化状态随基因表达的波动呈现动态的过程,表现出与基因表达量波动基本一致的波动趋势。展开更多
AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MG...AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction(MSPPCR) in gastric biopsy samples from uninfected or H.pylori-infected children(n = 50),from adults with chronic gastritis(n = 97) and from adults with gastric cancer(n = 92).MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene(β actin).MSI analysis was performed by screening MSI markers at 4 loci(Bat-25,Bat-26,D17S250 and D2S123) with PCR;PCR products were analysed by single strand conformation polymorphism followed by silver staining.Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher's exact test,and statistical significance for expression analysis was assessed using an unpaired Student's t-test.RESULTS:Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children,regardless of H.pylori infection status.The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H.pylori infection(P < 0.05);this region was methylated in 66% of gastric cancer patients,and the difference in the percentage of methylated samples between these patients and those from H.pylori-infected chronic gastritis patients was statistically significant(P < 0.05).MLH1 methylation frequencies among H.pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%,respectively.We observed methylation of the MLH1 promoter(39%) and increased MSI levels(68%) in samples from gastric cancer patients in comparison to samples from H.pylori-infected adult chronic gastritis patients(P < 0.001 and P < 0.01,respectively).The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H.pylori-positive chronic gastrit展开更多
基金Supported by A 2-year grant of the Greek Ministry of Health and Welfare,No.111K/56
文摘AIM:To investigate aberrant DNA methylation of CpG islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma(tu-bular or villous/tubulovillous)patients,and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1(hMLH1),Cyclin-dependent kinase inhibitor 2A(CDKN2A/p16),and O-6-methylguanine DNA methyltransferase(MGMT),as well as their rela- tion to MSI. RESULTS:The frequency of promoter methylation for each locus increased in the sequence healthy tissue/adenoma/carcinoma.MGMT showed the highest frequency in each group.MGMT and CDKN2A/p16 presented a statistically significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas(tubular vs tubullovillous and villous adenomas).All patients with tubulovillous/villous adenomas,as well as all colorectal cancer patients,showed promoter methylation in at least one of the examined loci.These findings suggest a potentially crucial role for methylation in the polyp/adenoma to cancer progres- sion in colorectal carcinogenesis.MSI and methylation seem to be interdependent,as simultaneous hMLH1, CDKN2A/p16,and MGMT promoter methylation was present in 8/9 colorectal cancer patients showing the MSI phenotype. CONCLUSION:Methylation analysis of hMLH1,CD- KN2A/p16,and MGMT revealed specific methylation profiles for tubular adenomas,tubulovillous/villous adenomas,and colorectal cancers,supporting the use of these alterations in assessment of colorectal tumorigenesis.
基金supported by NSFC Joint Research Fund for Hong Kong and Macao Young Scholars(No.30928012)National Natural Science Foundation of China(No.81071634,81172582,and 30801344)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.
文摘脂联素(Adiponectin)是至今发现的唯一与肥胖呈负相关的脂肪细胞特异性蛋白,是调控生物体的能量稳态、葡萄糖代谢和脂肪代谢的脂源性细胞因子之一。生物信息学分析发现,adiponectin基因启动子区-1500～-1350bp是CpG位点的富集区域。为了进一步研究脂联素基因的表达调控研究,文章从表观遗传学角度出发,通过Real-time PCR与甲基化特异性PCR(Methylation special PCR,MSP)的方法对脂联素基因的表达及其启动子区的甲基化状况进行了分析。结果表明,在adiponectin基因启动子区CG富集的区域(-1500～-1350bp)中,90日龄长白猪大多去甲基化(83%),90日龄蓝塘猪部分去甲基化(33%),成年蓝塘猪全是高度甲基化(100%),成年长白猪部分去甲基化(33%)。甲基化与去甲基化过程主要发生在某些特定CpG位点。脂联素基因在猪肌肉组织中以高度甲基化状态为主,这一结果与该基因在肌肉组织中表达量相吻合。以上结果提示,随个体发育,脂联素基因的甲基化状态随基因表达的波动呈现动态的过程,表现出与基因表达量波动基本一致的波动趋势。
基金Supported by The Fundacao de Amparo a Pesquisa do Estado de Sao Paulo,No.2009/01813-0 and 2008/02678-6the Conselho Nacional de Desenvolvimento Científico e Tecnológico,No. 471088/2007-2
文摘AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction(MSPPCR) in gastric biopsy samples from uninfected or H.pylori-infected children(n = 50),from adults with chronic gastritis(n = 97) and from adults with gastric cancer(n = 92).MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene(β actin).MSI analysis was performed by screening MSI markers at 4 loci(Bat-25,Bat-26,D17S250 and D2S123) with PCR;PCR products were analysed by single strand conformation polymorphism followed by silver staining.Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher's exact test,and statistical significance for expression analysis was assessed using an unpaired Student's t-test.RESULTS:Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children,regardless of H.pylori infection status.The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H.pylori infection(P < 0.05);this region was methylated in 66% of gastric cancer patients,and the difference in the percentage of methylated samples between these patients and those from H.pylori-infected chronic gastritis patients was statistically significant(P < 0.05).MLH1 methylation frequencies among H.pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%,respectively.We observed methylation of the MLH1 promoter(39%) and increased MSI levels(68%) in samples from gastric cancer patients in comparison to samples from H.pylori-infected adult chronic gastritis patients(P < 0.001 and P < 0.01,respectively).The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H.pylori-positive chronic gastrit
基金Supported by National Natural Science Foundation of China(81071989,81272760)Natural Science Foundation of Guangdong Province(S2011010004178)Science and Technology Program of Guangdong Province(c1221020700008)~~
