title: Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study.
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.
authors: CHU de Dijon, Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Université de Bourgogne, Dijon, France.
authors: Julien
authors: J
authors: Thevenon
authors: Abderrahmane
authors: A
authors: Bourredjem
authors: Laurence
authors: L
authors: Faivre
authors: Catherine
authors: C
authors: Cardot-Bauters
authors: Alain
authors: A
authors: Calender
authors: Arnaud
authors: A
authors: Murat
authors: Sophie
authors: S
authors: Giraud
authors: Patricia
authors: P
authors: Niccoli
authors: Marie-Françoise
authors: MF
authors: Odou
authors: Françoise
authors: F
authors: Borson-Chazot
authors: Anne
authors: A
authors: Barlier
authors: Catherine
authors: C
authors: Lombard-Bohas
authors: Eric
authors: E
authors: Clauser
authors: Antoine
authors: A
authors: Tabarin
authors: Béatrice
authors: B
authors: Parfait
authors: Olivier
authors: O
authors: Chabre
authors: Emilie
authors: E
authors: Castermans
authors: Albert
authors: A
authors: Beckers
authors: Philippe
authors: P
authors: Ruszniewski
authors: Morgane
authors: M
authors: Le Bras
authors: Brigitte
authors: B
authors: Delemer
authors: Philippe
authors: P
authors: Bouchard
authors: Isabelle
authors: I
authors: Guilhem
authors: Vincent
authors: V
authors: Rohmer
authors: Bernard
authors: B
authors: Goichot
authors: Philippe
authors: P
authors: Caron
authors: Eric
authors: E
authors: Baudin
authors: Philippe
authors: P
authors: Chanson
authors: Lionel
authors: L
authors: Groussin
authors: Hélène
authors: H
authors: Du Boullay
authors: Georges
authors: G
authors: Weryha
authors: Pierre
authors: P
authors: Lecomte
authors: Alfred
authors: A
authors: Penfornis
authors: Hélène
authors: H
authors: Bihan
authors: Françoise
authors: F
authors: Archambeaud
authors: Véronique
authors: V
authors: Kerlan
authors: Françoise
authors: F
authors: Duron
authors: Jean-Marc
authors: JM
authors: Kuhn
authors: Bruno
authors: B
authors: Vergès
authors: Michel
authors: M
authors: Rodier
authors: Michel
authors: M
authors: Renard
authors: Jean-Louis
authors: JL
authors: Sadoul
authors: Christine
authors: C
authors: Binquet
authors: Pierre
authors: P
authors: Goudet
mesh_terms: D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D009154:Mutation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: C559371:JunD protein, human; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun