TY - JOUR T1 - Genomic expression differences between cutaneous cells from red hair color individuals and black hair color individuals based on bioinformatic analysis. JF - Oncotarget Y1 - 2017 A1 - Puig-Butille, Joan Anton A1 - Gimenez-Xavier, Pol A1 - Visconti, Alessia A1 - Nsengimana, Jérémie A1 - Garcia-Garcia, Francisco A1 - Tell-Marti, Gemma A1 - Escamez, Maria José A1 - Newton-Bishop, Julia A1 - Bataille, Veronique A1 - Del Rio, Marcela A1 - Dopazo, Joaquin A1 - Falchi, Mario A1 - Puig, Susana KW - Adult KW - Coculture Techniques KW - Computational Biology KW - gene expression KW - Genetic Predisposition to Disease KW - Genomics KW - Hair Color KW - Humans KW - Keratinocytes KW - Melanocytes KW - Middle Aged KW - Phenotype KW - Receptor, Melanocortin, Type 1 AB -

The MC1R gene plays a crucial role in pigmentation synthesis. Loss-of-function MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk. Cultured cutaneous cells bearing loss-of-function MC1R variants show a distinct gene expression profile compared to wild-type MC1R cultured cutaneous cells. We analysed the gene signature associated with RHC co-cultured melanocytes and keratinocytes by Protein-Protein interaction (PPI) network analysis to identify genes related with non-functional MC1R variants. From two detected networks, we selected 23 nodes as hub genes based on topological parameters. Differential expression of hub genes was then evaluated in healthy skin biopsies from RHC and black hair color (BHC) individuals. We also compared gene expression in melanoma tumors from individuals with RHC versus BHC. Gene expression in normal skin from RHC cutaneous cells showed dysregulation in 8 out of 23 hub genes (CLN3, ATG10, WIPI2, SNX2, GABARAPL2, YWHA, PCNA and GBAS). Hub genes did not differ between melanoma tumors in RHC versus BHC individuals. The study suggests that healthy skin cells from RHC individuals present a constitutive genomic deregulation associated with the red hair phenotype and identify novel genes involved in melanocyte biology.

VL - 8 UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=14140&path%5B%5D=45094 IS - 7 U1 - https://www.ncbi.nlm.nih.gov/pubmed/28030792?dopt=Abstract ER - TY - JOUR T1 - Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer. JF - Oncotarget Y1 - 2013 A1 - Puig-Butille, Joan Anton A1 - Escamez, Maria José A1 - Garcia-Garcia, Francisco A1 - Tell-Marti, Gemma A1 - Fabra, Angels A1 - Martínez-Santamaría, Lucía A1 - Badenas, Celia A1 - Aguilera, Paula A1 - Pevida, Marta A1 - Joaquín Dopazo A1 - Del Rio, Marcela A1 - Puig, Susana AB - 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. UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1444&path%5B%5D=1824 ER - TY - JOUR T1 - Role of CPI-17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film-forming medical device containing photolyase and UV filters. JF - Exp Dermatol Y1 - 2013 A1 - Puig-Butille, Joan Anton A1 - Malvehy, Josep A1 - Potrony, Miriam A1 - Trullas, Carles A1 - Garcia-Garcia, Francisco A1 - Dopazo, Joaquin A1 - Puig, Susana KW - Administration, Topical KW - Adult KW - Aged KW - Aged, 80 and over KW - Biopsy KW - Deoxyribodipyrimidine Photo-Lyase KW - Female KW - Gene Expression Profiling KW - Gene Expression Regulation, Enzymologic KW - Gene Expression Regulation, Neoplastic KW - Homeostasis KW - Humans KW - Inflammation KW - Intracellular Signaling Peptides and Proteins KW - Liposomes KW - Male KW - Middle Aged KW - Muscle Proteins KW - Phenotype KW - Phosphoprotein Phosphatases KW - Reactive Oxygen Species KW - Skin KW - Skin Neoplasms KW - Ultraviolet Rays AB -

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6-4 photoproducts (6-4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film-forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over-expression of the CPI-17 gene, and a dependence on the initial expression level was observed (P = 0.001). Low CPI-17 levels were directly associated with pro-inflammatory genes such as TNF (P = 0.012) and IL-1B (P = 0.07). Our results suggest a role for CPI-17 in restoring skin homoeostasis in CFC lesions.

VL - 22 IS - 7 U1 - https://www.ncbi.nlm.nih.gov/pubmed/23800065?dopt=Abstract ER -