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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.
Hum Mol Genet. 2013 May 15; 22(10):1940-8.HM

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+Show Affiliations

CHU de Dijon, Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Université de Bourgogne, Dijon, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23376981

Citation

Thevenon, Julien, 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, vol. 22, no. 10, 2013, pp. 1940-8.
Thevenon J, Bourredjem A, Faivre L, 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. Hum Mol Genet. 2013;22(10):1940-8.
Thevenon, J., Bourredjem, A., Faivre, L., Cardot-Bauters, C., Calender, A., Murat, A., Giraud, S., Niccoli, P., Odou, M. F., Borson-Chazot, F., Barlier, A., Lombard-Bohas, C., Clauser, E., Tabarin, A., Parfait, B., Chabre, O., Castermans, E., Beckers, A., Ruszniewski, P., ... Goudet, P. (2013). 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, 22(10), 1940-8. https://doi.org/10.1093/hmg/ddt039
Thevenon J, 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. Hum Mol Genet. 2013 May 15;22(10):1940-8. PubMed PMID: 23376981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study. AU - Thevenon,Julien, AU - Bourredjem,Abderrahmane, AU - Faivre,Laurence, AU - Cardot-Bauters,Catherine, AU - Calender,Alain, AU - Murat,Arnaud, AU - Giraud,Sophie, AU - Niccoli,Patricia, AU - Odou,Marie-Françoise, AU - Borson-Chazot,Françoise, AU - Barlier,Anne, AU - Lombard-Bohas,Catherine, AU - Clauser,Eric, AU - Tabarin,Antoine, AU - Parfait,Béatrice, AU - Chabre,Olivier, AU - Castermans,Emilie, AU - Beckers,Albert, AU - Ruszniewski,Philippe, AU - Le Bras,Morgane, AU - Delemer,Brigitte, AU - Bouchard,Philippe, AU - Guilhem,Isabelle, AU - Rohmer,Vincent, AU - Goichot,Bernard, AU - Caron,Philippe, AU - Baudin,Eric, AU - Chanson,Philippe, AU - Groussin,Lionel, AU - Du Boullay,Hélène, AU - Weryha,Georges, AU - Lecomte,Pierre, AU - Penfornis,Alfred, AU - Bihan,Hélène, AU - Archambeaud,Françoise, AU - Kerlan,Véronique, AU - Duron,Françoise, AU - Kuhn,Jean-Marc, AU - Vergès,Bruno, AU - Rodier,Michel, AU - Renard,Michel, AU - Sadoul,Jean-Louis, AU - Binquet,Christine, AU - Goudet,Pierre, Y1 - 2013/01/31/ PY - 2013/2/5/entrez PY - 2013/2/5/pubmed PY - 2013/11/2/medline SP - 1940 EP - 8 JF - Human molecular genetics JO - Hum Mol Genet VL - 22 IS - 10 N2 - 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. SN - 1460-2083 UR - https://www.unboundmedicine.com/medline/citation/23376981/Higher_risk_of_death_among_MEN1_patients_with_mutations_in_the_JunD_interacting_domain:_a_Groupe_d'etude_des_Tumeurs_Endocrines__GTE__cohort_study_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddt039 DB - PRIME DP - Unbound Medicine ER -