1. New susceptibility loci for cutaneous melanoma risk and progression revealed using a porcine model
- Author
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Bourneuf, Emmanuelle, Jordi Estellé, Jordi, Blin, Amandine, Créchet, Francoise, Schneider, Maria-Del-Pilar, Gilbert, Hélène, Brossard, Myriam, Vaysse, Amaury, Lathrop, Mark, Vincent-Naulleau, Silvia, Demenais, Florence, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), DRF/IRCM/SREIT/LREG, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM), Taxonomie - Collections (TC), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (COMUE) (USPC), Innovation Centre, P&G, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT), and Université de Toulouse (UT)
- Subjects
pig ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,[SDV]Life Sciences [q-bio] ,melanoma ,GWAS ,[INFO]Computer Science [cs] ,comparative genomics ,Research Paper ,biomedical model - Abstract
International audience; Despite major advances, it is estimated that a large part of melanoma predisposing genes remains to be discovered. Animal models of spontaneous diseases are valuable tools and experimental crosses can be used to identify and fine-map new susceptibility loci associated with melanoma. We performed a Genome-Wide Association Study (GWAS) of melanoma occurrence and progression (clinical ulceration and presence of metastasis) in a porcine model of spontaneous melanoma, the MeLiM pig. Five loci on chromosomes 2, 5, 7, 8 and 16 showed genome-wide significant associations ( p < 5 × 10 –6 ) with either one of these phenotypes. Suggestive associations ( p < 5 × 10 –5 ) were also found at 16 additional loci. Moreover, comparison of the porcine results to those reported by human melanoma GWAS indicated shared association signals notably at CDKAL1 and TERT loci but also nearby CCND1 , FTO, PLA2G6 and TMEM 38B-RAD23B loci. Extensive search of the literature revealed a potential key role of genes at the identified porcine loci in tumor invasion ( DST , PLEKHA5, CBY1 , LIMK2 and ETV5 ) and immune response modulation ( ETV5 , HERC3 and DICER1 ) of the progression phenotypes. These biological processes are consistent with the clinico-pathological features of MeLiM tumors and can open new routes for future melanoma research in humans.
- Published
- 2018
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