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Mammalian Genome

, Volume 22, Issue 9–10, pp 602–612 | Cite as

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

  • Emmanuelle BourneufEmail author
  • Zhi-Qiang Du
  • Jordi Estellé
  • Hélène Gilbert
  • Françoise Créchet
  • Guillaume Piton
  • Denis Milan
  • Claudine Geffrotin
  • Mark Lathrop
  • Florence Demenais
  • Claire Rogel-Gaillard
  • Silvia Vincent-Naulleau
Article

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.

Keywords

Melanoma Quantitative Trait Locus Quantitative Trait Locus Analysis Cutaneous Melanoma Porcine Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was funded by La Ligue Nationale Contre le Cancer, in the framework of the projects of Genetic Epidemiology 2006–2008 and 2010–2011. ZQD was a postdoctoral fellow from INRA Animal Genetics Department and JE was a postdoctoral fellow from the INRA program “Jeunes Docteurs.” The authors are thankful to several people for microsatellite genotyping: Catherine Denis at UMR GABI, Micaëlla Germain at Labogena, and Julie Mautord at Plateforme Génomique in Toulouse. The authors also acknowledge Diana Zelenika for SNP genotyping organization and Patrice Dehais for providing SNP information.

Supplementary material

335_2011_9334_MOESM1_ESM.doc (217 kb)
Supplementary material 1 (DOC 263 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Emmanuelle Bourneuf
    • 1
    • 2
    • 3
    Email author
  • Zhi-Qiang Du
    • 4
  • Jordi Estellé
    • 1
    • 2
    • 3
  • Hélène Gilbert
    • 2
    • 5
  • Françoise Créchet
    • 1
    • 2
    • 3
  • Guillaume Piton
    • 1
    • 2
    • 3
  • Denis Milan
    • 6
  • Claudine Geffrotin
    • 1
    • 2
    • 3
  • Mark Lathrop
    • 7
  • Florence Demenais
    • 8
  • Claire Rogel-Gaillard
    • 1
    • 2
    • 3
  • Silvia Vincent-Naulleau
    • 1
    • 2
    • 3
  1. 1.INRA, UMR Génétique Animale et Biologie Intégrative (GABI), Equipe Génétique Immunité SantéJouy-en-JosasFrance
  2. 2.AgroParisTech, UMR GABIJouy-en-JosasFrance
  3. 3.CEA, DSV/iRCM/SREIT/LREGJouy-en-JosasFrance
  4. 4.Department of Animal Science and Center for Integrated Animal GenomicsIowa State UniversityAmesUSA
  5. 5.INRA, UMR Génétique Animale et Biologie Intégrative (GABI)Equipe Génétique du PorcJouy-en-JosasFrance
  6. 6.INRA, UMR 444 Laboratoire de Génétique CellulaireCastanet-TolosanFrance
  7. 7.Centre National de Génotypage, CEA, DSV/IG/CNG, 2, rue Gaston CrémieuxEvryFrance
  8. 8.INSERM U946, Fondation Jean-Dausset-CEPHParisFrance

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