Research Papers:

New susceptibility loci for cutaneous melanoma risk and progression revealed using a porcine model

Emmanuelle Bourneuf _, Jordi Estellé, Amandine Blin, Françoise Créchet, Maria del Pilar Schneider, Hélène Gilbert, Myriam Brossard, Amaury Vaysse, Mark Lathrop, Silvia Vincent-Naulleau and Florence Demenais

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Oncotarget. 2018; 9:27682-27697. https://doi.org/10.18632/oncotarget.25455

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Emmanuelle Bourneuf1,2, Jordi Estellé1,2, Amandine Blin2,3,5, Françoise Créchet1,2, Maria del Pilar Schneider2,8, Hélène Gilbert6, Myriam Brossard3,4, Amaury Vaysse3,4, Mark Lathrop7, Silvia Vincent-Naulleau1,2 and Florence Demenais3,4

1CEA, DRF/iRCM/SREIT/LREG, Jouy-en-Josas, France

2GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France

3INSERM, UMR-946, Genetic Variation and Human Diseases Unit, Paris, France

4Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France

5Outils et Méthodes de la Systématique Intégrative, OMSI–UMS 2700, CNRS MNHN, Muséum National d’Histoire Naturelle, Paris, France

6GenPhyse, INRA, Université de Toulouse, INPT, ENVT, Castanet Tolosan, France

7McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada

8Present address: Ipsen Innovation, Les Ulis, France

Correspondence to:

Emmanuelle Bourneuf, email: [email protected]

Keywords: melanoma; biomedical model; pig; GWAS; comparative genomics

Received: November 09, 2017     Accepted: May 05, 2018     Published: June 12, 2018


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 TMEM38B-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.

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