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Hypermethylation Status (hypermethylation + status)
Selected AbstractsHypermethylation status of APC inversely correlates with the presence of submucosal invasion in laterally spreading colorectal tumorsMOLECULAR CARCINOGENESIS, Issue 1 2008Kazuo Hashimoto Abstract Little is known about epigenetic alterations in laterally spreading colorectal tumors (LSTs). The goal of the present study was to elucidate the epigenetic background of LSTs and compare the methylation status of DNA CpG islands (CGIs) with clinicopathologic features. Methylation of MINT1, MINT2, MINT31, p16, O6 -methylguanine-DNA methyltransferase (MGMT), adenomatous polyposis coli (APC), and human MutL homologue 1 (hMLH1) in 42 LSTs was assessed by methylation-specific polymerase chain reaction (MSP) and compared with clinicopathologic parameters. The frequency of hypermethylation was 12.5% (4/32) for MINT1, 40.0% (16/40) for MINT2, 25.0% (10/40) for MINT31, 25.7% (9/35) for p16, 7.7% (3/39) for hMLH1, 26.5% (9/34) for MGMT, and 35.9% (14/39) for APC. APC methylation was inversely associated with submucosal invasion (P,=,0.034), which was not found in any of 14 LST cases with APC methylation, whereas submucosal invasion was present in 8 of 25 (32.0%) cases without APC methylation. These data suggest that hypermethylation of APC could be a predictive marker for the absence of submucosal invasion of LSTs. © 2007 Wiley-Liss, Inc. [source] E-cadherin expression in early gastric carcinoma and correlation with lymph node metastasisJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2007Dong Yi Kim MD Abstract Objective Abnormal expression of E-cadherin plays an important role in the differentiation and progression of gastric carcinoma. However, the relationship between molecular changes in E-cadherin and metastasis in early gastric carcinoma (EGC) is poorly understood. Materials and Methods Sixty cases of EGC with or without lymph node metastasis (30 node-positive cases and 30 node-negative cases) were investigated to evaluate hypermethylation status using bisulfate-MSP and immunohistochemistry using antibody against E-cadherin. Results Twenty-seven (45.0%) of 60 primary EGCs exhibited methylation in the CpG island of E-cadherin. Abnormal expression of E-cadherin was significantly correlated with patient age, tumor size, Lauren classification, differentiation, and lymph node metastasis. Using multiple logistic regression analysis, two factors were independent, statistically significant parameters associated with lymph node metastasis: abnormal expression of E-cadherin (risk ratio, 2.62; 95% confidence interval, 0.917,7.457; P,<,0.05) and lymphatic invasion (risk ratio, 8.11; 95% confidence interval, 1.612,40.766; P,<,0.05). Conclusion Our results suggest that methylation of E-cadherin is a frequent, early event in gastric carcinoma progression, and is correlated significantly with downregulated E-cadherin expression. Inactivation of E-cadherin might be involved in metastasis in EGC and play an important role in microscopic differentiation. J. Surg. Oncol. 2007;96:429,435. © 2007 Wiley-Liss, Inc. [source] Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis,THE JOURNAL OF PATHOLOGY, Issue 2 2007Y Hori Abstract Renal cell carcinoma (RCC) is more frequently observed in patients on dialysis than in patients with normal renal function. However, the mechanism underlying carcinogenesis in RCC patients on dialysis is still unclear. We hypothesized that oxidative stress affects patients on dialysis and generates new neoplasms, and therefore analysed the correlation between the influences of various markers of oxidative stress and carcinogenesis in those patients. We evaluated the immunohistochemical expression of oxidative stress markers, such as iNOS, 8-OHdG, and COX-2 in 42 cases on dialysis and 51 cases with normal renal function as a control. The methylation status of p16INK4a, p14ARF, VHL, and RASSF1A was analysed together with clinicopathological factors. Histologically, the papillary type was observed more frequently in dialysis RCC than in sporadic RCC. Immunohistochemically, overexpression of iNOS (p < 0.0001) and COX-2 (p = 0.0002) was more frequently observed in dialysis RCC. Furthermore, the 8-OHdG labelling index was significantly higher in dialysis RCC than in sporadic RCC. Hypermethylation of p16INK4a was more frequently found in dialysis RCC (p < 0.05). However, no significant correlations between oxidative stress markers and DNA hypermethylation status were observed. The overexpression of iNOS, COX-2, and 8-OHdG in dialysis RCC suggests that patients on dialysis are affected by oxidative stress and that this effect plays an important role in the genesis of dialysis RCC. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] HRK inactivation associated with promoter methylation and LOH in prostate cancerTHE PROSTATE, Issue 1 2008Tomonori Higuchi Abstract OBJECTIVES Recent studies in selected human tumors have demonstrated reduced expression of HRK with hypermethylation. Because no similar study has been performed specifically in prostatic lesions, we examined whether the methylation status of HRK is altered in prostate cancers. METHODS We chose to analyze the hypermethylation status of HRK, the expression of HRK protein and mRNA with 12q13.1 loss of heterozygosity (LOH) and with p53 mutation, and lesion apoptotic indices as determined by transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end-labeling (TUNEL) assays in 53 prostate cancers. RESULTS Twenty of the 53 prostate cancers (38%) demonstrated hypermethylation in either the promoter or in exon 1 and, more significantly, the loss of HRK expression observed in 14 cancers by immunohistochemistry (IHC) was associated with promoter methylation. In addition, high apoptotic indices in tumors were related to positive HRK expression. Prostate cancers demonstrating HRK methylation also showed methylation of multiple other genes, such as p14ARF, p16INK4a, O6 -MGMT, and GTS-P, but, with the exception of one case, p53 mutations were not detected. When compared to tumors having a Gleason score (GS) of 5,6, a significant difference in the apoptotic indices was found among prostate cancers of GS 7 (P,<,0.001) or GS 8,9 (P,=,0.007). We also detected a close correlation between the loss of HRK expression and decreased apoptosis in GS 5,6 and GS 7 tumors (P,=,0.008, P,<,0.001, respectively). CONCLUSIONS HRK appears to be inactivated principally by promoter hypermethylation in prostate cancers. We further suggest that the decreased expression of HRK may play an important role in tumor progression by modulating apoptotic cell death. Prostate 68: 105,113, 2008. © 2007 Wiley-Liss, Inc. [source] Methylation status of CpG islands in the promoter regions of signature genes during chondrogenesis of human synovium,derived mesenchymal stem cellsARTHRITIS & RHEUMATISM, Issue 5 2009Yoichi Ezura Objective Human synovium,derived mesenchymal stem cells (MSCs) can efficiently differentiate into mature chondrocytes. It has been suggested that DNA methylation is one mechanism that regulates human chondrogenesis; however, the methylation status of genes related to chondrogenic differentiation is not known. The purpose of this study was to investigate the CpG methylation status in human synovium,derived MSCs during experimental chondrogenesis, with a view toward potential therapeutic use in osteoarthritis. Methods Human synovium,derived MSCs were subjected to chondrogenic pellet culture for 3 weeks. The methylation status of 12 regions in the promoters of 10 candidate genes (SOX9, RUNX2, CHM1, FGFR3, CHAD, MATN4, SOX4, GREM1, GPR39, and SDF1) was analyzed by bisulfite sequencing before and after differentiation. The expression levels of these genes were analyzed by real-time reverse transcription,polymerase chain reaction. Methylation status was also examined in human articular cartilage. Results Bisulfite sequencing analysis indicated that 10 of the 11 CpG-rich regions analyzed were hypomethylated in human progenitor cells before and after 3 weeks of pellet culture, regardless of the expression levels of the genes. The methylation status was consistently low in SOX9, RUNX2, CHM1, CHAD, and FGFR3 following an increase in expression upon differentiation and was low in GREM1 and GPR39 following a decrease in expression upon chondrogenesis. One exceptional instance of a differentially methylated CpG-rich region was in a 1-kb upstream sequence of SDF1, the expression of which decreased upon differentiation. Paradoxically, the hypermethylation status of this region was reduced after 3 weeks of pellet culture. Conclusion The DNA methylation levels of CpG-rich promoters of genes related to chondrocyte phenotypes are largely kept low during chondrogenesis in human synovium,derived MSCs. [source] | ||||||||||