Research Papers:

Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer.

María José Escamez, Francisco Garcia-Garcia, Gemma Tell-Marti, Angels Fabra, Lucía Martínez-Santamaría, Celia Badenas, Paula Aguilera, Marta Pevida, Joaquín Dopazo, Marcela del Río and Susana Puig _

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Oncotarget. 2014; 5:1439-1451. https://doi.org/10.18632/oncotarget.1444

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Joan Anton Puig-Butille1,2, María José Escámez3,4,5, Francisco Garcia-Garcia6,7, Gemma Tell-Marti 1, Àngels Fabra8, Lucía Martínez-Santamaría3,4,5, Celia Badenas1,2, Paula Aguilera1,2, Marta Pevida5,9, Joaquín Dopazo6,7,10, Marcela del Río3,4,5, Susana Puig1,2

1 Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d’Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain

2 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.

3 Regenerative Medicine Unit. Epithelial Biomedicine Division. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.

4 Department of Bioengineering. Universidad Carlos III (UC3M), Madrid, Spain.

5 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

6 Functional Genomics Node, National Institute of Bioinformatics, CIPF Valencia, Spain

7 Department of Bioinformatics, Centro de Investigación Príncipe Felipe, Valencia, Spain

8 Biological Clues of the Invasive and Metastatic Phenotype Group. Molecular Oncology Lab, IDIBELL, Barcelona, Spain

9 Tissue Engineering Unit. Centro Comunitario de Sangre y Tejidos del Principado de Asturias (CCST), Oviedo, Spain

10 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.


Susana Puig, email:

Keywords: Familial Melanoma, CDKN2A, MC1R, gene expression, p16, mutations

Received: September 25, 2013 Accepted: December 16, 2013 Published: December 16, 2013


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.

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