Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA109437 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide screen for promoter methylation in NSCLC identifies novel methylation markers for multiple malignancies
| PRJNA99053 | ENA
Project description:Background: DNA methylation is an important component of epigenetic modifications that influences the transcriptional machinery and is aberrant in many human diseases. In particular, dysregulation of promoter methylation in cancer has already been shown to be associated with repression of tumor suppressors and activation of oncogenes. In addition, detection of altered promoter methylation status is suitable for the design of diagnostic or prognostic tests. In this study we present a new methodological approach for the robust identification of promoter methylation markers and the first genome-wide study for the detection of methylation markers in melanoma. Methods and Findings: Genome-wide promoter methylation and gene expression of ten early passage melanoma cell strains are compared to newborn and adult normal melanocytes. For the identification of markers we applied linear mixed effect models (LME) in combination with a series of filters based on the localization of promoter methylation relative to the transcription start site, overall promoter CpG content, and differential gene expression. The aim of this methodology is to identify markers whose promoter differential methylation is likely to be functionally related to differential expression. We identified 76 markers, 68 hyper- and 8-hypo-methylated in melanomas (LME P<0.05). Promoter methylation profiles and differential expression of five of these markers were successfully validated. In addition, promoter demethylation following Aza treatment consistently restored expression of markers hyper-methylated in melanoma. Conclusions: The proposed methodology allows the identification of robust markers and can be applied to other experimental scenarios where promoter methylation is evaluated. More importantly, the list of markers represents the first systematic effort in the identification of methylation markers in melanoma. Many of the identified markers were not previously known to be regulated by promoter methylation and/or associated with this or other types of cancer.
2009-05-26 | GSE13706 | GEO
Project description:The implication of epigenetic alterations in the pathogenesis of melanoma is increasingly recognized. Here we performed genome-wide DNA methylation analysis of primary cutaneous melanoma and benign melanocytic naevus interrogating 14,495 genes using beadchip technology. This first genome-wide view of promoter methylation in primary cutaneous melanoma revealed an array of recurrent DNA methylation alterations with potential diagnostic applications. Among 106 frequently hypermethylated genes there were many novel methylation targets and tumor suppressor genes. Highly recurrent methylation of the HOXA9, MAPK13, CDH11, PLEKHG6, PPP1R3C and CLDN11genes was established. Promoter methylation of MAPK13, encoding p38?, was present in 67% of primary and 85% of metastatic melanomas. Restoration of MAPK13 expression in melanoma cells exhibiting epigenetic silencing of this gene reduced proliferation, indicative of tumor suppressive functions. This study demonstrates that DNA methylation alterations are widespread in melanoma and suggests that epigenetic silencing of MAPK13 contributes to melanoma progression. Bisulphite converted genomic DNA from 5 fresh-frozen benign naevus and 24 fresh-frozen primary melanoma biopsy samples were hybridised to Illumina's Infinium HumanMethylation27 Beadchips
2013-04-24 | E-GEOD-45266 | biostudies-arrayexpress
Project description:The implication of epigenetic alterations in the pathogenesis of melanoma is increasingly recognized. Here we performed genome-wide DNA methylation analysis of primary cutaneous melanoma and benign melanocytic naevus interrogating 14,495 genes using beadchip technology. This first genome-wide view of promoter methylation in primary cutaneous melanoma revealed an array of recurrent DNA methylation alterations with potential diagnostic applications. Among 106 frequently hypermethylated genes there were many novel methylation targets and tumor suppressor genes. Highly recurrent methylation of the HOXA9, MAPK13, CDH11, PLEKHG6, PPP1R3C and CLDN11genes was established. Promoter methylation of MAPK13, encoding p38?, was present in 67% of primary and 85% of metastatic melanomas. Restoration of MAPK13 expression in melanoma cells exhibiting epigenetic silencing of this gene reduced proliferation, indicative of tumor suppressive functions. This study demonstrates that DNA methylation alterations are widespread in melanoma and suggests that epigenetic silencing of MAPK13 contributes to melanoma progression.
2013-04-24 | GSE45266 | GEO
Project description:A screen to identify novel tumor suppressor genes silenced by methylation in melanoma
| PRJNA102651 | ENA
Project description:Tumor suppressor genes (TSGs) are sometimes inactivated by transcriptional silencing through promoter hypermethylation. To identify novel methylated TSGs in melanoma, we carried out global mRNA expression profiling on a panel of 12 melanoma cell lines treated with a combination of 5-Aza-2-deoxycytidine (5AzadC) and an inhibitor of histone deacetylase, Trichostatin A. Reactivation of gene expression after drug treatment was assessed using Illumina whole-genome microarrays. After qRT-PCR confirmation, we followed up 8 genes (AKAP12, ARHGEF16, ARHGAP27, ENC1, PPP1R3C, PPP1R14C, RARRES1, and TP53INP1) by quantitative DNA methylation analysis using mass spectrometry of base-specific cleaved amplification products in panels of melanoma cell lines and fresh tumors. PPP1R3C, ENC1, RARRES1, and TP53INP1, showed reduced mRNA expression in 35–59% of the melanoma cell lines compared to melanocytes and which was correlated with a high proportion of promoter methylation (>40–60%). The same genes also showed extensive promoter methylation in 6–25% of the tumor samples, thus confirming them as novel candidate TSGs in melanoma.
2011-10-03 | GSE32492 | GEO
Project description:Tumor suppressor genes (TSGs) are sometimes inactivated by transcriptional silencing through promoter hypermethylation. To identify novel methylated TSGs in melanoma, we carried out global mRNA expression profiling on a panel of 12 melanoma cell lines treated with a combination of 5-Aza-2-deoxycytidine (5AzadC) and an inhibitor of histone deacetylase, Trichostatin A. Reactivation of gene expression after drug treatment was assessed using Illumina whole-genome microarrays. After qRT-PCR confirmation, we followed up 8 genes (AKAP12, ARHGEF16, ARHGAP27, ENC1, PPP1R3C, PPP1R14C, RARRES1, and TP53INP1) by quantitative DNA methylation analysis using mass spectrometry of base-specific cleaved amplification products in panels of melanoma cell lines and fresh tumors. PPP1R3C, ENC1, RARRES1, and TP53INP1, showed reduced mRNA expression in 35–59% of the melanoma cell lines compared to melanocytes and which was correlated with a high proportion of promoter methylation (>40–60%). The same genes also showed extensive promoter methylation in 6–25% of the tumor samples, thus confirming them as novel candidate TSGs in melanoma. We sought to identify melanoma TSGs silenced by promoter methylation by carrying out an array-based analysis in a well-annotated panel of 12 cell lines after combined treatment with 5AzadC and an inhibitor of histone deacetylase, Trichostatin A (TSA). Expression profiles were generated for each cell line before and after drug treatment using Illumina Sentrix Human-6 Expression version 2 BeadChips. Genes reactivated in all 12 cell lines were removed from further analysis since they are likely responding to drug treatment as part of the ‘‘cellular stress response,’’ or due to promoter demethylation of genes normally silenced in the melanocytic lineage. Genes were further filtered to identify those with an average of >4-fold increased expression in at least four samples in the panel of 12 lines and >10-fold increase in at least one of the cell lines.
2011-10-02 | E-GEOD-32492 | biostudies-arrayexpress
Project description:Genome-wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma
| PRJNA193430 | ENA
Project description:Epigenetic regulation of tumor suppressor genes (TSGs) has been shown to play a central role in melanomagenesis. Integrating gene expression and methylation array analysis we identified novel candidate TSGs frequently methylated in melanoma. We validated the methylation status of the most promising TSGs using the highly sensitive, specific and comprehensive Sequenom Epityper assay in a large panel of melanoma cell lines and resected melanomas, and compared the findings with that from cultured melanocytes. We found transcript levels of UCHL1, COL1A2, THBS1 and TNFRSF10D were inversely correlated with promoter methylation. The effect of this methylation on expression was confirmed at the protein level. Identification of these candidate TSGs and how their silencing is related to melanoma development will increase our understanding of the etiology of this cancer and may provide tools for its early diagnosis. Analysed samples consisted of 11 melanoma cell lines and 1 neonatal foreskin melanocyte pool as a reference. Melanoma cell lines overlap with members of the DNA copy number analysis series GSE9003 and expression profiling series GSE7127 . The matching copy number data GEO samples IDs are noted in characteristics: Matching CN Sample ID and characteristics: Matching expn Sample ID columns respectively.
2011-10-24 | E-GEOD-28356 | biostudies-arrayexpress
Project description:Methylation of CpG islands associated with genes can affect the expression of the proximal gene, and methylation of non associated CpG islands correlates to genomic instability. This epigenetic modification has been shown to be important in many pathologies, from development and disease to cancer. We report the development of a novel high-resolution microarray that detects the methylation status of over 25,000 CpG islands in the human genome. Experiments were performed to demonstrate low system noise in the methodology and that the array probes have a high signal to noise ratio. Methylation measurements between different cell lines were validated demonstrating the accuracy of measurement. We then identified alterations in CpG islands, both those associated with gene promoters, as well as non-promoter associated islands in a set of breast and ovarian tumors. We demonstrate that this methodology accurately identifies methylation profiles in cancer and in principle it can differentiate any CpG methylation alterations and can be adapted to analyze other species. We have developed a method to profile genome wide methylation. 7 ovarian normal samples and 11 tumor samples from other individuals were analyzed for CpG methylation. After inter array normalization, the tumor samples were taken together and the methylation compared to that of the normal samples to identify regions of the CpG islands that are significantly altered between the two datasets. Some of these regions were validated for their methylation as a proof of principle for the method.
2010-05-19 | E-GEOD-15747 | biostudies-arrayexpress