title: Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer.
abstract: Germline mutations in CDKN2A and/or red hair color variants in MC1R genes are associated with an increased susceptibility to develop cutaneous melanoma or non melanoma skin cancer. We studied the impact of the CDKN2A germinal mutation p.G101W and MC1R variants on gene expression and transcription profiles associated with skin cancer. To this end we set-up primary skin cell co-cultures from siblings of melanoma prone-families that were later analyzed using the expression array approach. As a result, we found that 1535 transcripts were deregulated in CDKN2A mutated cells, with over-expression of immunity-related genes (HLA-DPB1, CLEC2B, IFI44, IFI44L, IFI27, IFIT1, IFIT2, SP110 and IFNK) and down-regulation of genes playing a role in the Notch signaling pathway. 3570 transcripts were deregulated in MC1R variant carriers. In particular, genes related to oxidative stress and DNA damage pathways were up-regulated as well as genes associated with neurodegenerative diseases such as Parkinson's, Alzheimer and Huntington. Finally, we observed that the expression signatures indentified in phenotypically normal cells carrying CDKN2A mutations or MC1R variants are maintained in skin cancer tumors (melanoma and squamous cell carcinoma). These results indicate that transcriptome deregulation represents an early event critical for skin cancer development.
authors.affiliation: Melanoma Unit, Hospital Clinic and IDIBAPS (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain.
authors.forename: Joan Anton
authors.initials: JA
authors.lastname: Puig-Butille
authors.forename: María José
authors.initials: MJ
authors.lastname: Escámez
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Garcia
authors.forename: Gemma
authors.initials: G
authors.lastname: Tell-Marti
authors.forename: Àngels
authors.initials: À
authors.lastname: Fabra
authors.forename: Lucía
authors.initials: L
authors.lastname: Martínez-Santamaría
authors.forename: Celia
authors.initials: C
authors.lastname: Badenas
authors.forename: Paula
authors.initials: P
authors.lastname: Aguilera
authors.forename: Marta
authors.initials: M
authors.lastname: Pevida
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.forename: Marcela
authors.initials: M
authors.lastname: del Río
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D044102:Receptor, Melanocortin, Type 1
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