Similar Datasets
Project description:To understand the global methylation patterns in MCC cell lines
2021-09-15 | GSE184206 | GEO
Project description:To understand the global methylation pattern in MCC
2021-09-15 | GSE176466 | GEO
Project description:Viral Status Predicts Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma [Methylation]
| PRJNA763581 | ENA
Project description:Viral Status Predicts Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma
| PRJNA763577 | ENA
Project description:Viral Status Predicts Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma [RNA-Seq]
| PRJNA736335 | ENA
Project description:Background: Clear cell renal cell carcinomas (ccRCCs) display divergent clinical phenotypes. Up to one third of patients with local disease at diagnosis will progress. Therefore, it is a need to identify patients at risk for recurrence. In the present study, we analyzed genome-wide promoter DNA methylation at diagnosis in relation to clinicopathological parameters, in order to identify DNA methylation profiles associated with risk for progress. Method: DNA methylation status in 155,931 CpGs located in gene promoter regions was analyzed by Illumina HumanMethylation450K arrays in diagnostic tissue samples from 115 ccRCC patients. Methylation profiles were compared with genetic aberrations and clinicopathological parameters. Results: The tumors separated into two clusters based on genome-wide promoter methylation status. The tumors in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) 72 % in cluster A vs 26 % in cluster B, p < 0.001). When metastasis-status (M0/M1) and cluster A/B status at diagnosis were combined, we found poor survival in M1 patients regardless of cluster A/B status (pCSS5yr 9 % vs 6 %). In M0 patients, the cluster status clearly separated in survival (pCSS5yr 81 % vs 17 %; p < 0.001). We identified a methylation profile of 398 CpGs that was associated with progress of disease, which included differently methylated CpG sites in the SMAD6, SOCS3 and MX2 genes. An integrated genomic and epigenomic analysis revealed significant correlations between the total number of genetic aberrations and hypermethylated CpGs (R = 0.435, p > 0.001), and predicted mitotic age (R = 0.407, p < 0.001). Conclusion: DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction and therapy stratification.
2019-01-23 | GSE113501 | GEO
Project description:Genome-wide DNA methylation profiling of 786-0 RCC cells treated with decitabine (100nM and 300nM) or DMSO vehicle. The Illumina Infinium HumanMethylation EPIC BeadChip was used to obtain DNA methylation profiles across approximately 850K CpGs.
2020-06-01 | GSE146179 | GEO
Project description:Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with neuroendocrine features. Although the role of epigenetic in tumorigenesis has been documented in most type of cancer, it is overlooked in MCC. The treatment options for MCC is limited and the five-year survival rate remains as low as 33%. In addition, recent studies have suggested multiple mechanisms of epigenetic dysregulation that may contribute to loss H3K27me3 and the tumorigenesis in MCC but not well studied. In this study, we conducted DNA methylation analysis of an existing retrospective cohort of clinically annotated MCC samples, which included samples from 8 primary tumors, three metastatic skin tumors, four metastatic lymph node tumors, and five paired normal tissue samples. Global DNA methylation profile was performed using Illumina Infinium MethylationEPIC array. Two MCC cell lines were also analyzed for DNA methylation and gene expression (RNA-seq) to confirm the correlation between DNA methylation and gene expression for MCC. Our analysis revealed 24,497 loci (14,456 genes) that showed significantly different DNA methylation pattern in the four groups (ANOVA p-value < 0.05 and standard deviation of mean of groups > 0.25) namely adjacent normal, primary tumor, metastatic skin, and metastatic lymph node in MCC patients. By GO terms analysis, the genes correlated with DNA methylation alteration associated with nervous system, cell adhesion, signal transduction, and development pathways. We also observed 870 probes differentially methylated in MCPyV positive and MCPyV negative tumor (FDR adjusted p-value < 0.05 and delta change greater than 0.4 or less than -0.4). Furthermore, using expression and DNA methylation data from two MCC cell lines (MS1 and MCC13) as validation, we identified 964 MCC specific genes directly regulated by DNA methylation either at promoter or gene body, which are highly enriched in nervous system related pathways. By this approach, we not only identify DNA methylation markers for MCC and MCPyV status but also genes regulated by DNA methylation in MCC, MCPyV status, and neuroendocrine features. Most importantly, our results may also suggest overexpression of KDM6B and EZHIP by loss of DNA methylation in their promoter may contribute to loss of H3K27me3 in MCC. In addition, we observed the DNA methylation profile of MS1 resembled MCC patient sample, while DNA methylation profile of MCC13 cell line was similar to small cell lung carcinoma (SCLC), which suggested that MCC13 cell line may originally come from SCLC. Taken together, we have demonstrated dramatic DNA methylation alteration along with four unique patterns in normal, primary and metastatic MCC. Our finding provides DNA methylation markers not only for diagnosis or prognosis of MCC and MCPyV status but also correlate gene expression status of MCC specific genes with important functional roles in MCC tumorigenesis, MCPyV expression, neuroendocrine feature and H3K27me3 status. The identification of DNA methylation alteration in MCC also provides foundation for potential implication of epigenetic therapy for MCC patients.
2021-07-13 | GSE160878 | GEO
Project description:Merkel cell carcinoma (MCC) is a neuroendocrine tumor either induced by integration of the Merkel cell polyomavirus into the cell genome or by accumulation of UV-light-associated mutations (VP-MCC and UV-MCC). Whether VP- and UV-MCC have the same or different cellular origins is unclear; with mesenchymal or epidermal origins discussed. DNA-methylation patterns have a proven utility in determining cellular origins of cancers. Therefore, we used this approach to uncover evidence regarding the cell of origin of classical VP- and UV-MCC cell lines, i.e., cell lines with a neuroendocrine growth pattern (n = 9 and n = 4, respectively). Surprisingly, we observed high global similarities in the DNA-methylation of UV- and VP-MCC cell lines. CpGs of lower methylation in VP-MCC cell lines were associated with neuroendocrine marker genes such as SOX2 and INSM1, or linked to binding sites of EZH2 and SUZ12 of the polycomb repressive complex 2, i.e., genes with an impact on carcinogenesis and differentiation of neuroendocrine cancers. Thus, the observed differences appear to be rooted in viral compared to mutation-driven carcinogenesis rather than distinct cells of origin. To test this hypothesis, we used principal component analysis, to compare DNA-methylation data from different epithelial and non-epithelial neuroendocrine cancers and established a scoring model for epithelial and neuroendocrine characteristics. Subsequently, we applied this scoring model to the DNA-methylation data of the VP- and UV-MCC cell lines, revealing that both clearly scored as epithelial cancers. In summary, our comprehensive analysis of DNA-methylation suggests a common epithelial origin of UV- and VP-MCC cell lines.
| S-EPMC8724008 | biostudies-literature
Project description:Merkel cell carcinoma (MCC) is the most aggressive skin cancer. Recently, it was demonstrated that human Merkel cell polyomavirus (MCV) is clonally integrated in approximately 80% of MCC tumors. However, direct evidence for whether oncogenic viral proteins are needed for the maintenance of MCC cells is still missing. To address this question, we knocked down MCV T-antigen (TA) expression in MCV-positive MCC cell lines using three different short hairpin RNA (shRNA)-expressing vectors targeting exon 1 of the TAs. The MCC cell lines used include three newly generated MCV-infected cell lines and one MCV-negative cell line from MCC tumors. Notably, all MCV-positive MCC cell lines underwent growth arrest and/or cell death upon TA knockdown, whereas the proliferation of MCV-negative cell lines remained unaffected. Despite an increase in the number of annexin V-positive, 7-amino-actinomycin D (7-AAD)-negative cells upon TA knockdown, activation of caspases or changes in the expression and phosphorylation of Bcl-2 family members were not consistently detected after TA suppression. Our study provides the first direct experimental evidence that TA expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC.
| S-EPMC2898224 | biostudies-literature