Project description:Germline mutations in CDKN2A and/or red hair colour variants in MC1R genes are associated with an increased susceptibility to develop cutaneous melanoma. To investigate the impact of germinal p.G101W CDKN2A mutation and MC1R variants on gene expression and transcription profiles associated to skin cancer and melanoma in particular, we set-up primary skin cultures from twins belonging to the melanoma prone-families with and without these genomic features. were analyzed using expression array methodology. Overall, 1535 transcripts were deregulated in CDKN2A mutated cells, finding overexpression of immunity-related genes (HLA-DPB1, CLEC2B, IFI44, IFI44L, IFI27, IFIT1, IFIT2, SP110 and IFNK) and downregulation of genes playing a role in the Notch signaling pathway. 3570 transcripts were deregulated in carriers of MC1R variants. In this case, upregulated genes were involved in oxidative stress and DNA damage pathways as well as in neurodegenerative diseases such as Parkinson’s, Alzheimer and Huntington. In contrast, downregulated genes were associated with pigmentation synthesis/transport and angiogenesis. By using a coculture system, this study identified key molecular functions and/or pathways that are deregulated due to alterations in melanoma susceptibility genes which in turn, could be involved in initiation/progression of the disease. 12 samples total. Several experimental groups: with and without genomic features (CDKN2A, MC1R).

2013-12-31 | E-GEOD-44805 | biostudies-arrayexpress

Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

Project description:This SuperSeries is composed of the following subset Series: GSE38622: Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis [telogen]. GSE38623: Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis [Anagen] GSE38624: Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis [Bmal1 KO] Refer to individual Series

2012-08-01 | E-GEOD-38625 | biostudies-arrayexpress

Rare germline copy number variations and disease susceptibility in familial melanoma

Project description:Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and SNP arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanoma-prone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g. PARP1, CDKN2A) or co-segregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare co-segregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.

2016-12-01 | GSE85010 | GEO

Interleukin enhancer-binding factor 2 promotes cell proliferation and DNA damage response in metastatic melanoma

Project description:This study aimed to understand the role of ILF2 upregulation in metastatic melanoma cutaneous progression and DNA damage response. The goal of RPPA analysis was to determine the protein expression profiles in DP-0574 and IM-0223 melanoma cell lines with ILF2 overexpression (ILF2-OV) or control empty vector (EV). By analysis of RPPA in both metastatic melanoma cell lines, we found that ILF2-OV controls significantly increased RAD50 expression.

2022-04-15 | GSE159692 | GEO

Capturing the biological impact of the melanoma susceptibility genes CDKN2A and MC1R in cocultured keratinocytes and melanocytes

2013-12-31 | GSE44805 | GEO

UVR induced DNA-damage in Cutaneous Melanoma

Project description:Ultraviolet radiation–induced DNA damage is prognostic for outcome in melanoma

| PRJEB30941 | ENA

Regulation of the RNAPII Pool Is Integral to the DNA Damage Response

Project description:Regulation of the RNAPII Pool Is Integral to the DNA Damage Response

| PRJNA600921 | ENA