02299nas a2200253   4500008004100000022001400041245013400055210006900189260001600258520136900274100003001643700002601673700002901699700002201728700001801750700003401768700001901802700002001821700001801841700002101859700002101880700001701901856012701918       2013                        eng d  a1949-255300aCapturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer.0 aCapturing the biological impact of CDKN2A and MC1R genes as an e  c2013 Dec 163 aGermline 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.1 aPuig-Butille, Joan, Anton1 aEscamez, Maria, José1 aGarcia-Garcia, Francisco1 aTell-Marti, Gemma1 aFabra, Angels1 aMartínez-Santamaría, Lucía1 aBadenas, Celia1 aAguilera, Paula1 aPevida, Marta1 aDopazo, Joaquín1 aDel Rio, Marcela1 aPuig, Susana  uhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1444&path%5B%5D=1824