A MITF germline mutation predisposes to melanoma and renal cell carcinoma
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PROVIDER: EGAS00000000048 | EGA |
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A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
Bertolotto Corine C Lesueur Fabienne F Giuliano Sandy S Strub Thomas T de Lichy Mahaut M Bille Karine K Dessen Philippe P d'Hayer Benoit B Mohamdi Hamida H Remenieras Audrey A Maubec Eve E de la Fouchardière Arnaud A Molinié Vincent V Vabres Pierre P Dalle Stéphane S Poulalhon Nicolas N Martin-Denavit Tanguy T Thomas Luc L Andry-Benzaquen Pascale P Dupin Nicolas N Boitier Françoise F Rossi Annick A Perrot Jean-Luc JL Labeille Bruno B Robert Caroline C Escudier Bernard B Caron Olivier O Brugières Laurence L Saule Simon S Gardie Betty B Gad Sophie S Richard Stéphane S Couturier Jérôme J Teh Bin Tean BT Ghiorzo Paola P Pastorino Lorenza L Puig Susana S Badenas Celia C Olsson Hakan H Ingvar Christian C Rouleau Etienne E Lidereau Rosette R Bahadoran Philippe P Vielh Philippe P Corda Eve E Blanché Hélène H Zelenika Diana D Galan Pilar P Aubin François F Bachollet Bertrand B Becuwe Céline C Berthet Pascaline P Bignon Yves Jean YJ Bonadona Valérie V Bonafe Jean-Louis JL Bonnet-Dupeyron Marie-Noëlle MN Cambazard Fréderic F Chevrant-Breton Jacqueline J Coupier Isabelle I Dalac Sophie S Demange Liliane L d'Incan Michel M Dugast Catherine C Faivre Laurence L Vincent-Fétita Lynda L Gauthier-Villars Marion M Gilbert Brigitte B Grange Florent F Grob Jean-Jacques JJ Humbert Philippe P Janin Nicolas N Joly Pascal P Kerob Delphine D Lasset Christine C Leroux Dominique D Levang Julien J Limacher Jean-Marc JM Livideanu Cristina C Longy Michel M Lortholary Alain A Stoppa-Lyonnet Dominique D Mansard Sandrine S Mansuy Ludovic L Marrou Karine K Matéus Christine C Maugard Christine C Meyer Nicolas N Nogues Catherine C Souteyrand Pierre P Venat-Bouvet Laurence L Zattara Hélène H Chaudru Valérie V Lenoir Gilbert M GM Lathrop Mark M Davidson Irwin I Avril Marie-Françoise MF Demenais Florence F Ballotti Robert R Bressac-de Paillerets Brigitte B
Nature 20111019 7375
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 (M ...[more]
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Project description:In this study, we report here a rare case of polycythemia and cRCC in the same patient, which may be helpful in understanding clinical features and molecular mechanisms underlying VHL-mutation-associated cRCC and polycythemia induced by germline mutation of HIF2A. Firstly, we identified a rare but well studied germline mutation resulting in polycythemia in HIF2A (c.1609G>A, p.Gly537Trp) in the blood of the patient and his daughter. Meanwhile, we identified an inactivating VHL mutation (c.391A>T, p.N131Y), as well as TP53 mutation(c.977A>T, p.E326V) and mTOR mutation(c.7498A>T, p.I2500F) in renal cancer tissue. Moreover, protein levels of VHL, HIF1A, HIF2A, EPO, and VEGF estimated by immunohistochemical staining substantiated hyperactivation of the oxygen-sensing pathway. In addition, we identified 158 somatic SNP/indel mutations, including 90 missense/nonsense/splice/stop-loss mutations by whole-exome sequencing (WES) of the tumor specimen and matched normal DNA.
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