Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Analysis of paired primary and metastatic cell lines identifies common DNA methylation changes in melanoma metastasis.

ABSTRACT: Using 1 melanocyte and 6 melanoma cell line (3 pair of primary and metastatic), we generated base-resolution DNA methylation maps to document DNA methylation drivers of melanoma metastasis. Here we generated single-nucleotide resoultion DNA methylation map of a total of 7 cell lines using Reduced Representation Bisulfite Sequencing (RRBS)

ORGANISM(S): Homo sapiens

SUBMITTER: Aniruddha Chatterjee

PROVIDER: E-GEOD-70621 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis.

Chatterjee Aniruddha A Stockwell Peter A PA Ahn Antonio A Rodger Euan J EJ Leichter Anna L AL Eccles Michael R MR

Oncotarget 20170101 4

Epigenetic alterations are increasingly implicated in metastasis, whereas very few genetic mutations have been identified as authentic drivers of cancer metastasis. Yet, to date, few studies have identified metastasis-related epigenetic drivers, in part because a framework for identifying driver epigenetic changes in metastasis has not been established. Using reduced representation bisulfite sequencing (RRBS), we mapped genome-wide DNA methylation patterns in three cutaneous primary and metastat ...[more]

PMID: 28030832

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Project description:Melanoma genomes are often characterized by large numbers of sunlight-induced mutations. However, epigenetic alterations, in the form of aberrant DNA methylation patterns, are also abundant. Using MIRA-seq, we have carried out a comprehensive characterization of the DNA methylome in a series of metastatic melanoma samples and catalogued the methylation changes relative to normal melanocytes, the presumed cells of origin for these tumors. Individual melanoma tumors contained up to several thousand hypermethylated regions. We discovered 179 tumor-specific methylation peaks that were present in all (27/27) melanomas and may lend themselves as effective disease biomarkers, and 3124 methylation peaks were present in >40% of the tumors. We specifically examined the relationship between presence of the Polycomb mark, H3K27me3 in melanocytes and tumor-specific DNA methylation in melanoma. We found that 150 of the approximately 1,200 tumor-associated methylation peaks near transcription start sites (TSS) were H3K27me3-marked in melanocytes. Notably, DNA methylation in melanoma was specific for distinct H3K27me3 peaks rather than for H3K27me3-enriched regions with broad genomic coverage. Yet, there were also numerous H3K27me3 peak-associated TSS regions that were completely resistant to DNA methylation in tumors. Furthermore, a rather large group of genes became methylated in melanoma but lacked H3K27me3 in melanocytes. There was no relationship between presence of BRAF V600 mutations and the number of methylation peaks in individual tumors. Gene expression analysis showed a strong signature of upregulated immune response genes in melanomas presumably as a result of lymphocyte infiltration. Genes down-regulated in tumors were enriched for melanocyte differentiation and pigmentation factors. Overall, there was limited correlation between tumor-associated DNA methylation changes and changes in gene expression although distinct melanocyte differentiation genes including KIT, PAX3 and SOX10 became methylated and downregulated in melanoma. Using MIRA-Seq, DNA methylation profiles of 27 malignant melanomas and 3 primary cultured melanocyte samples were determined

Dataset Information

Analysis of paired primary and metastatic cell lines identifies common DNA methylation changes in melanoma metastasis.

Publications

Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis.

Similar Datasets

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