Genetic and functional evaluation of MITF as a candidate gene for cutaneous melanoma predisposition in pigs.
Mamm Genome
; 22(9-10): 602-12, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21626174
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Predisposição Genética para Doença
/
Fator de Transcrição Associado à Microftalmia
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Melanoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mamm Genome
Assunto da revista:
GENETICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
França