RNA-sequencing of melanoma celllines compared to normal human melanocytes (NHEMs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE284779 | GEO | 2024/12/20
REPOSITORIES: GEO
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Project description:DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. Here, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients and compared the methylation status with melanoma tissues from the same individuals. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports and indicated that NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease. Our results highlight the importance of using matched fresh melanoma and melanocyte samples in epigenetic studies. Illumina Infinium 450k Human Methylation Beadchip
2018-11-29 | GSE122909 | GEO
Project description:DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. Here, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients and compared the methylation status with melanoma tissues from the same individuals. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports and indicated that NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease. Our results highlight the importance of using matched fresh melanoma and melanocyte samples in epigenetic studies. illumina HumanHT-12_v4 BeadChip
2018-11-29 | GSE122907 | GEO
Project description:The study aims to identify differences in miRNA expression during melanoma development. Therefore, normal human epidermal melanocytes (NHEM) were de-differentiated into melanoblast-related cells (MBrCs) to model processes during embryonic differentiation and to compare them to the tumorigenic phenotype in melanoma development.
2021-05-26 | GSE174334 | GEO
Project description:Normal human epidermal melanocytes (NHEM, purchased from PromoCell) were culture for one (7 days) or two weeks (14 days) and subsequently, total RNA was isolated and cDNA array analysis was performed. The array was used to determine general gene expression patterns in primary melanocytes. Moreover, gene expression alterations during cell culturing (one or two weeks) can be detected. Finally, the gene expression array is used to compared gene expression paterns with melanoma cell and tissue gene expression patterns or with other primary cell lines.
2020-11-16 | GSE108969 | GEO
Project description:Spotted oligonucleotide microarrays were used to assess global differential gene expression comparing normal human melanocytes with six independent melanoma cell strains from advanced lesions. The data, validated at the protein level for selected genes, confirmed the overexpression in melanoma cells relative to normal melanocytes of several genes in the growth factor/receptor family that confer growth advantage and metastasis. In addition, novel pathways and patterns of associated expression in melanoma cells not reported before emerged. Six melanoma cultures and two melanocyte cultures. The melanoma cultures are considered, for the purposes of this investigation, replicates from the point of view that they are all melanomas. Three of the melanomas were replicated once or twice in addition.
2010-07-01 | E-GEOD-4576 | biostudies-arrayexpress
Project description:Most cancer genomics papers to date have focused on aberrations in genomic DNA and protein-coding transcripts. However, around 50% of transcripts have no coding potential and may exist as non-coding RNA. We performed RNA-seq in BRAFv600e melanoma skin cancer and on melanocytes over-expressing oncogenic BRAF to catalog transcriptome remodeling. We discovered that BRAF regulates expression of 1027 protein coding transcripts, 39 annotated lncRNAs and 70 novel transcripts. Many of the novel transcripts are lncRNAs. We used an indepenedent dataset to interrogate our novel transcripts and found that the novel lncRNA BANCR is a BRAF-regulated lncRNA recurrently upregulated in melanoma. Knockdown of BANCR impairs melanoma cell migration. Whole transcriptome RNA-seq followed assembly to Refseq/Gencode and de novo transcript assembly. RNA-seq performed on: 2 BRAFv600e melanomas, melanocytes+RFP control and melanocytes + BRAFv600e. We discovered protein-coding transcripts, annotated ncRNAs and novel transcripts (including lncRNAs) regulated by BRAFv600e also coordinately expressed in melanoma.
2012-04-28 | E-GEOD-33092 | biostudies-arrayexpress
Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
2022-01-17 | GSE181748 | GEO
Project description:Ultraviolet (UV) radiation is a major melanoma risk factor, yet underlying mechanisms remain poorly understood. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon-response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-gamma (IFN-gamma), but not type-I interferons. IFN-gamma was produced by macrophages recruited to neonatal skin by UVB-induced chemokine receptor Ccr2 ligands. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-gamma blockade abolished macrophage-associated melanoma growth and survival. IFN-gamma-producing macrophages were identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-gamma in promoting melanocytic cell survival/immunoevasion, and suggest IFN-gamma-R signaling represents a novel therapeutic melanoma target. Biologic replicates of UVA- and UVB-treated mouse melanocytes, as well as untreated mouse melanocytes and mouse keratinocytes, were used to define melanocyte expression signatures associated with UV treatment.
2011-01-01 | E-GEOD-25164 | biostudies-arrayexpress
Project description:DNA methylation profiling of human melanocytes and melanoma cell lines. Goal was to identify hypermethylated gene promoters in melanoma Genomic DNA from 4 human melanoma cell lines and normal human epidermal melanocytes was subjected to methylated DNA immunoprecipitation (MeDIP) and hybridized to Agilent's G4489A Human Promoter ChIP-on-Chip Set 244K
2014-08-01 | E-GEOD-53801 | biostudies-arrayexpress
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. Genome-wide gene expression analysis of 17 melanomas and 3 melanocyte samples
2016-03-31 | E-GEOD-71747 | biostudies-arrayexpress