Reference : A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcino...
Scientific journals : Article
Life sciences : Genetics & genetic processes
http://hdl.handle.net/2268/110233
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
English
Bertolotto, Corine [> > > >]
Lesueur, Fabienne [> > > >]
Giuliano, Sandy [> > > >]
Strub, Thomas [> > > >]
de Lichy, Mahaut [> > > >]
Bille, Karine [> > > >]
Dessen, Philippe [> > > >]
d'Hayer, Benoit [> > > >]
Mohamdi, Hamida [> > > >]
Remenieras, Audrey [> > > >]
Maubec, Eve [> > > >]
de la Fouchardiere, Arnaud [> > > >]
Molinie, Vincent [> > > >]
Vabres, Pierre [> > > >]
Dalle, Stephane [> > > >]
Poulalhon, Nicolas [> > > >]
Martin-Denavit, Tanguy [> > > >]
Thomas, Luc [> > > >]
Andry-Benzaquen, Pascale [> > > >]
Dupin, Nicolas [> > > >]
Boitier, Francoise [> > > >]
Rossi, Annick [> > > >]
Perrot, Jean*-Luc [> > > >]
Labeille, Bruno [> > > >]
Robert, Caroline [> > > >]
Escudier, Bernard [> > > >]
Caron, Olivier [> > > >]
Brugieres, Laurence [> > > >]
Saule, Simon [> > > >]
Gardie, Betty [> > > >]
Gad, Sophie [> > > >]
Richard, Stephane [> > > >]
Couturier, Jerome [> > > >]
Teh, Bin Tean [> > > >]
Ghiorzo, Paola [> > > >]
Pastorino, Lorenza [> > > >]
Puig, Susana [> > > >]
Badenas, Celia [> > > >]
Olsson, Hakan [> > > >]
Ingvar, Christian [> > > >]
Rouleau, Etienne [> > > >]
Lidereau, Rosette [> > > >]
Bahadoran, Philippe [> > > >]
Vielh, Philippe [> > > >]
Corda, Eve [> > > >]
Blanche, Helene [> > > >]
Zelenika, Diana [> > > >]
Galan, Pilar [> > > >]
Aubin, Francois [> > > >]
Bachollet, Bertrand [> > > >]
Becuwe, Celine [> > > >]
Berthet, Pascaline [> > > >]
Bignon, Yves Jean [> > > >]
Bonadona, Valerie [> > > >]
Bonafe, Jean*-Louis [> > > >]
Bonnet-Dupeyron, Marie*-Noelle [> > > >]
Cambazard, Frederic [> > > >]
Chevrant-Breton, Jacqueline [> > > >]
Coupier, Isabelle [> > > >]
Dalac, Sophie [> > > >]
Demange, Liliane [> > > >]
d'Incan, Michel [> > > >]
Dugast, Catherine [> > > >]
Faivre, Laurence [> > > >]
Vincent-Fetita, Lynda [> > > >]
Gauthier-Villars, Marion [> > > >]
Gilbert, Brigitte [> > > >]
Grange, Florent [> > > >]
Grob, Jean*-Jacques [> > > >]
Humbert, Philippe [> > > >]
JANIN, Nicolas mailto [Centre Hospitalier Universitaire de Liège - CHU > > Génétique]
Joly, Pascal [> > > >]
Kerob, Delphine [> > > >]
Lasset, Christine [> > > >]
Leroux, Dominique [> > > >]
Levang, Julien [> > > >]
Limacher, Jean*-Marc [> > > >]
Livideanu, Cristina [> > > >]
Longy, Michel [> > > >]
Lortholary, Alain [> > > >]
Stoppa-Lyonnet, Dominique [> > > >]
Mansard, Sandrine [> > > >]
Mansuy, Ludovic [> > > >]
Marrou, Karine [> > > >]
Mateus, Christine [> > > >]
Maugard, Christine [> > > >]
Meyer, Nicolas [> > > >]
Nogues, Catherine [> > > >]
Souteyrand, Pierre [> > > >]
Venat-Bouvet, Laurence [> > > >]
Zattara, Helene [> > > >]
Chaudru, Valerie [> > > >]
Lenoir, Gilbert M [> > > >]
Lathrop, Mark [> > > >]
Davidson, Irwin [> > > >]
Avril, Marie*-Francoise [> > > >]
Demenais, Florence [> > > >]
Ballotti, Robert [> > > >]
Bressac-de Paillerets, Brigitte [> > > >]
2011
Nature
Nature Publishing Group
480
7375
94-8
Yes (verified by ORBi)
0028-0836
1476-4687
Basingstoke
United Kingdom
[en] So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (PsiKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
http://hdl.handle.net/2268/110233
10.1038/nature10539

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