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; Abderrahmane Bourredjem; Laurence Faivre; Catherine Cardot-Bauters; Alain Calender; Arnaud Murat; Sophie Giraud; Patricia Niccoli; Marie-Françoise Odou; Françoise Borson-Chazot; Anne Barlier; Catherine Lombard-Bohas; Eric Clauser; Antoine Tabarin; Béatrice Parfait; Olivier Chabre; Emilie Castermans; Albert Beckers; Philippe Ruszniewski; Morgane Le Bras; Brigitte Delemer; Philippe Bouchard; Isabelle Guilhem; Vincent Rohmer; Bernard Goichot; Philippe Caron; Eric Baudin; Philippe Chanson; Lionel Groussin; Hélène Du Boullay; Georges Weryha; Pierre Lecomte; Alfred Penfornis; Hélène Bihan; Françoise Archambeaud; Véronique Kerlan; Françoise Duron; Jean-Marc Kuhn; Bruno Vergès; Michel Rodier; Michel Renard; Jean-Louis Sadoul; Christine Binquet; Pierre Goudet

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 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

1 UJF - Université Joseph Fourier - Grenoble 1

2 Immunovirologie et polymorphisme génétique

3 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques

4 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)

5 Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents

6 CRCL - Centre de Recherche en Cancérologie de Lyon

7 Centre de médecine nucléaire

8 CRN2M - Centre de recherche en neurobiologie - neurophysiologie de Marseille

9 Hôpital Edouard Herriot [CHU - HCL]

10 BORDEAUX - Endocrino - Service d'Endocrinologie

11 Inserm U745 - Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux

12 BCI - Biologie du Cancer et de l'Infection

13 LIEGE - Endocrino - Service d'Endocrinologie

14 Department of Gastroenterology

15 PVM - Pathologie et virologie moléculaire

16 Service d'Endocrinologie - Diabète - Nutrition [Reims]

17 LMGE - Laboratoire Microorganismes : Génome et Environnement

18 Centre Hospitalier Universitaire [Rennes]

19 ANGERS - Endocrino - Service d'Endocrinologie

20 Département de Médecine Interne et Nutrition

21 TOULOUSE - Endocrino - Service d'Endocrinologie

22 Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique

23 IGR - Institut Gustave Roussy

24 Médecine nucléaire

Département d'imagerie médicale [Gustave Roussy]

25 Service d'Endocrinologie [CHRU Nancy]

26 TOURS - Endocrino - Service d'Endocrinologie

27 Service de diabétologie - endocrinologie

28 PCVP / CARDIO - Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920)

29 APHP - Assistance publique - Hôpitaux de Paris (AP-HP)

30 Service de Médecine interne B, Endocrinologie, Diabète, Maladies métaboliques [CHU Limoges]

31 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale

32 CHRU - Endocrino - Service d'Endocrinologie

33 Service de Diabétologie

34 Service des maladies métaboliques et endocriniennes

35 NICE - Endocrino - Service d'Endocrinologie

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

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https://hal.univ-brest.fr/hal-00935869
Contributor : Ghislaine Calvez <>
Submitted on : Friday, January 24, 2014 - 11:21:23 AM
Last modification on : Thursday, July 11, 2019 - 4:04:02 PM

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

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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.

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