Publication:
DNA Repair and Immune Response Pathways Are Deregulated in Melanocyte-Keratinocyte Co-cultures Derived From the Healthy Skin of Familial Melanoma Patients

dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Tissue Engineering and Regenerative Medicine (TERMeG)es
dc.contributor.authorPotrony, Miriam
dc.contributor.authorHaddad, Tariq Sami
dc.contributor.authorTell Marti, Gemma
dc.contributor.authorGiménez Xavier, Pol
dc.contributor.authorLeón Canseco, Carlos
dc.contributor.authorPevida, Marta
dc.contributor.authorMateu, Judit
dc.contributor.authorBadenas, Celia
dc.contributor.authorCarrera, Cristina
dc.contributor.authorMalvehy, Josep
dc.contributor.authorAguilera, Paula
dc.contributor.authorGonzalez Llames, Sara
dc.contributor.authorEscámez Toledano, María José
dc.contributor.authorPuig-Butille, J.A.
dc.contributor.authorRío Nechaevsky, Marcela del
dc.contributor.authorPuig, Susana
dc.contributor.funderComunidad de Madrides
dc.contributor.funderEuropean Commissionen
dc.contributor.funderMinisterio de Economía y Competitividad (España)es
dc.contributor.funderUniversidad Carlos III de Madrides
dc.date.accessioned2022-03-22T09:52:29Z
dc.date.available2022-03-22T09:52:29Z
dc.date.issued2021-10-01
dc.description.abstractFamilial melanoma accounts for 10% of cases, being CDKN2A the main high-risk gene. However, the mechanisms underlying melanomagenesis in these cases remain poorly understood. Our aim was to analyze the transcriptome of melanocyte-keratinocyte co-cultures derived from healthy skin from familial melanoma patients vs. controls, to unveil pathways involved in melanoma development in at-risk individuals. Accordingly, primary melanocyte-keratinocyte co-cultures were established from the healthy skin biopsies of 16 unrelated familial melanoma patients (8 CDKN2A mutant, 8 CDKN2A wild-type) and 7 healthy controls. Whole transcriptome was captured using the SurePrint G3 Human Microarray. Transcriptome analyses included: differential gene expression, functional enrichment, and protein-protein interaction (PPI) networks. We identified a gene profile associated with familial melanoma independently of CDKN2A germline status. Functional enrichment analysis of this profile showed a downregulation of pathways related to DNA repair and immune response in familial melanoma (P less than 0.05). In addition, the PPI network analysis revealed a network that consisted of double-stranded DNA repair genes (including BRCA1, BRCA2, BRIP1, and FANCA), immune response genes, and regulation of chromosome segregation. The hub gene was BRCA1. In conclusion, the constitutive deregulation of BRCA1 pathway genes and the immune response in healthy skin could be a mechanism related to melanoma risk.en
dc.description.sponsorshipThe main funding of this project came from the intramural project Papel del estrés oxidativo en el desarrollo de Melanoma Familiar y otras ER comunes con predisposición al desarrollo de neoplasias cutáneas financed by Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), of the Instituto de Salud Carlos III, Spain, co-financed by European Development Regional Fund A way to achieve Europe ERDF. The research at the Melanoma Unit in Barcelona is partially funded by Spanish Fondo de Investigaciones Sanitarias Grants PI15/00716 and PI15/00956, of the Instituto de Salud Carlos III, Spain, co-financed by European Development Regional Fund A way to achieve Europe ERDF; AGAUR 2017_SGR_1134 of the Catalan Government, Spain; European Commission under the 6th Framework Programme, Contract No. LSHC-CT-2006- 018702 (GenoMEL) and by the European Commission under the 7th Framework Programme, Diagnoptics; The National Cancer Institute (NCI) of the US National Institute of Health (NIH) (CA83115); a grant from Fundació La Marató de TV3 201331- 30, Catalonia, Spain; a grant from Fundación Científica de la Asociación Española Contra el Cáncer GCB15152978SOEN, Spain, and CERCA Programme/Generalitat de Catalunya. Part of the work was carried out at the Esther Koplowitz Center, Barcelona. The UC3M-CIEMAT-CIBERER-IISFJD research is mainly supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2017-86810-R) and from the Community of Madrid (AvanCell-CM S2017/BMD- 3692) which are co-funded with European Regional Development Funds (ERDF). TH was currently recipient of a PhD Fellowship at Radboud University Medical Center in the Netherlands funded by the Dutch Cancer Society (KWF) (10602).en
dc.format.extent8
dc.identifier.bibliographicCitationPotrony, M., Haddad, T. S., Tell-Martí, G., Gimenez-Xavier, P., Leon, C., Pevida, M., Mateu, J., Badenas, C., Carrera, C., Malvehy, J., Aguilera, P., Llames, S., Escámez, M. J., Puig-Butillé, J. A., del Río, M., & Puig, S. (2021). DNA Repair and Immune Response Pathways Are Deregulated in Melanocyte-Keratinocyte Co-cultures Derived From the Healthy Skin of Familial Melanoma Patients. In Frontiers in Medicine (Vol. 8). Frontiers Media SA.en
dc.identifier.doihttps://doi.org/10.3389/fmed.2021.692341
dc.identifier.issn2296-858X
dc.identifier.publicationfirstpage1
dc.identifier.publicationlastpage8
dc.identifier.publicationtitleFrontiers in Medicineen
dc.identifier.publicationvolume8
dc.identifier.urihttps://hdl.handle.net/10016/34433
dc.identifier.uxxiAR/0000030369
dc.language.isoengen
dc.publisherFrontiers Media SAen
dc.relation.projectIDGobierno de España. SAF2017-86810-Res
dc.relation.projectIDComunidad de Madrid. S2017/BMD-3692es
dc.relation.projectIDGobierno de España. PI15/00716es
dc.relation.projectIDGobierno de España. PI15/00956es
dc.relation.projectIDinfo:eu-repo/grantAgreement/LSHC-CT-2006- 018702en
dc.relation.projectIDinfo:eu-repo/grantAgreement/NIH/CA83115en
dc.relation.projectIDComunidad de Madrid. AvanCell-CM S2017/BMD- 3692es
dc.rights© 2021 Potrony, Haddad, Tell-Martí, Gimenez-Xavier, Leon, Pevida, Mateu, Badenas, Carrera,Malvehy, Aguilera, Llames, Escámez, Puig-Butillé, del Río and Puig.en
dc.rightsAtribución 3.0 España*
dc.rights.accessRightsopen accessen
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subject.ecienciaBiología y Biomedicinaes
dc.subject.otherCanceren
dc.subject.otherDna repairen
dc.subject.otherFamilial melanomaen
dc.subject.otherGeneticsen
dc.subject.otherImmune responseen
dc.subject.otherSkinen
dc.subject.otherTranscriptomeen
dc.titleDNA Repair and Immune Response Pathways Are Deregulated in Melanocyte-Keratinocyte Co-cultures Derived From the Healthy Skin of Familial Melanoma Patientsen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
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