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Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study.

Julien Thevenon 1, 2 Abderrahmane Bourredjem 3 Laurence Faivre 4 Catherine Cardot-Bauters Alain Calender 5, 6 Arnaud Murat Sophie Giraud 5 Patricia Niccoli Marie-Françoise Odou Françoise Borson-Chazot 7 Anne A. Barlier 8 Catherine Lombard-Bohas 6, 9 Eric Clauser Antoine Tabarin 10 Béatrice Parfait 11 Olivier Chabre 12 Emilie Castermans Albert Beckers 13 Philippe Ruszniewski 14 Morgane Le Bras 15 Brigitte Delemer 16 Philippe Bouchard 17 Isabelle Guilhem 18 Vincent Rohmer 19 Bernard Goichot 20 Philippe Caron 21 Eric Baudin 22, 23, 24 Philippe Chanson 22 Lionel Groussin Hélène Du Boullay Georges Weryha 25 Pierre Lecomte 26 Alfred Penfornis 27, 28 Hélène Bihan 29 Françoise Archambeaud 30 Véronique Kerlan 31, 32 Françoise Duron Jean-Marc Kuhn Bruno Vergès 33 Michel Rodier 34 Michel Renard Jean-Louis Sadoul 35 Christine Binquet 3 Pierre Goudet 
24 Médecine nucléaire
Département d'imagerie médicale [Gustave Roussy]
Abstract : Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.
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Submitted on : Friday, January 24, 2014 - 11:21:23 AM
Last modification on : Monday, November 28, 2022 - 10:38:07 AM

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Julien Thevenon, Abderrahmane Bourredjem, Laurence Faivre, Catherine Cardot-Bauters, Alain Calender, et al.. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study.. Human Molecular Genetics, 2013, 22 (10), pp.1940-8. ⟨10.1093/hmg/ddt039⟩. ⟨hal-00935869⟩



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