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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE44805 | GEO | 2013/12/31

SECONDARY ACCESSION(S): PRJNA191867

REPOSITORIES: GEO

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

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).

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