Genetic and functional evaluation of MITF as a candidate gene for cutaneous melanoma predisposition in pigs - Archive ouverte HAL
Article Dans Une Revue Mammalian Genome Année : 2011

Genetic and functional evaluation of MITF as a candidate gene for cutaneous melanoma predisposition in pigs

Résumé

Cutaneous melanoma arises from transformed melanocytes and is caused mainly by environmental effects such as ultraviolet radiation and to a lesser extent by predisposing genetic variants. Only a few susceptibility genes for cutaneous melanoma have been identified so far in human; therefore, animal models represent a valuable alternative for genetic studies of this disease. In a previous quantitative trait locus (QTL) study, several susceptibility regions were identified in a swine biomedical model, the MeLiM (Melanoblastoma-bearing Libechov minipig) pigs. This article details the fine-mapping of a QTL located on SSC13 (Sus scrofa chromosome 13) through an increase in marker density. New microsatellites were used to confirm the results of the first analysis, and MITF (microphthalmia-associated transcription factor) was selected as a candidate gene for melanoma development. A single-marker association analysis was performed with single-nucleotide polymorphisms (SNPs) spread over the locus, but it did not reveal a significant association with diverse melanoma-related traits. In parallel, MITF alternative transcripts were characterized and their expression was investigated in different porcine tissues. The obtained results showed a complex transcriptional regulation concordant with the one present in other mammals. Notably, the ratio between MITF+ and MITF− isoforms in melanoma samples followed the same pattern as in human tumors, which highlights the adequacy of the MeLiM pig as a model for human melanoma. In conclusion, although MITF does not seem to be the causal gene of the QTL initially observed, we do not exclude a prominent role of its transcription and function in the outbreak and evolution of the tumors observed in pigs.

Dates et versions

hal-01019749 , version 1 (07-07-2014)

Identifiants

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Emmanuelle Bourneuf, Zhi-Qiang Du, Jordi Estellé, Hélène Gilbert, Francoise Créchet, et al.. Genetic and functional evaluation of MITF as a candidate gene for cutaneous melanoma predisposition in pigs. Mammalian Genome, 2011, 22 (9-10), pp.602-612. ⟨10.1007/s00335-011-9334-6⟩. ⟨hal-01019749⟩
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