Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human melanoma cell lines treated with 5-Aza-2-deoxycytidine to identify novel tumor suppressor genes silenced by methylation in melanoma

ABSTRACT: Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Experiment Overall Design: RNA was isolated following 0 and 48 hours of 5AzadC treatment of melanocytes and six melanoma cell lines (MelJuSo, UACC 903, C8161, Neo6 C8161, WM1205, and WM35) and used for the reexpression microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Viswanathan Muthusamy

PROVIDER: E-GEOD-9118 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Epigenetic silencing of novel tumor suppressors in malignant melanoma.

Muthusamy Viswanathan V Duraisamy Sekhar S Bradbury C Matthew CM Hobbs Cara C Curley David P DP Nelson Betsy B Bosenberg Marcus M

Cancer research 20061201 23

Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified 17 genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Eigh ...[more]

PMID: 17145863

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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.

Dataset Information

Transcription profiling of human melanoma cell lines treated with 5-Aza-2-deoxycytidine to identify novel tumor suppressor genes silenced by methylation in melanoma

Publications

Epigenetic silencing of novel tumor suppressors in malignant melanoma.

Similar Datasets

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