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 -