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Bartsch, Detlef K.; Slater, Emily P.; Albers, Max; Knoop, Richard; Chaloupka, Brunhilde; Lopez, Caroline L.; Fendrich, Volker; Kann, Peter H.; Waldmann, Jens

Higher Risk of Aggressive Pancreatic Neuroendocrine Tumors in MEN1 Patients With MEN1 Mutations Affecting the CHES1 Interacting MENIN Domain

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  • Media type: E-Article
  • Title: Higher Risk of Aggressive Pancreatic Neuroendocrine Tumors in MEN1 Patients With MEN1 Mutations Affecting the CHES1 Interacting MENIN Domain
  • Contributor: Bartsch, Detlef K.; Slater, Emily P.; Albers, Max; Knoop, Richard; Chaloupka, Brunhilde; Lopez, Caroline L.; Fendrich, Volker; Kann, Peter H.; Waldmann, Jens
  • imprint: The Endocrine Society, 2014
  • Published in: The Journal of Clinical Endocrinology & Metabolism
  • Language: English
  • DOI: 10.1210/jc.2013-4432
  • ISSN: 0021-972X; 1945-7197
  • Keywords: Biochemistry (medical) ; Clinical Biochemistry ; Endocrinology ; Biochemistry ; Endocrinology, Diabetes and Metabolism
  • Origination:
  • Footnote:
  • Description: <jats:sec> <jats:title>Context:</jats:title> <jats:p>Sixty to 80% of multiple endocrine neoplasia type 1 (MEN1) patients develop pancreatic neuroendocrine neoplasias (pNENs), which reveal an aggressive behavior in 10%-20% of patients. Causative MEN1 mutations in the interacting domains of the encoded Menin protein directly alter its regulation abilities and may influence the phenotype.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>The objective of the study was the evaluation of an association between MEN1 mutations in different interacting domains of Menin and the phenotype of pNENs.</jats:p> </jats:sec> <jats:sec> <jats:title>Design:</jats:title> <jats:p>This was a retrospective analysis of a prospectively collected cohort of 71 genetically confirmed MEN1 patients at a tertiary referral center.</jats:p> </jats:sec> <jats:sec> <jats:title>Main Outcome Measures:</jats:title> <jats:p>Analysis of patients' characteristics and clinical phenotype of pNENs regarding the mutation type and its location in Menin interacting domains was measured.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Sixty-seven patients (93%) developed pNENs after a median follow-up of 134 months. Patients with mutations leading to loss of interaction (LOI) with the checkpoint kinase 1 (CHES1) interacting domain codons (428–610) compared with patients with mutations resulting in LOI with other domains (eg, JunD, Smad3) had significantly higher rates of functioning pNENs (70% vs 34%), malignant pNENs (59% vs 16%), and aggressive pNENs (37% vs 9%), respectively. Patients with CHES1-LOI also had an increased pNEN-related mortality (20% vs 4.5%). Neither gender, age, nor the ABO blood types were associated with the phenotype of pNENs.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>MEN1 patients with MEN1 mutations leading to CHES1-LOI have a higher risk of malignant pNENs with an aggressive course of disease and disease-related death.</jats:p> </jats:sec>
  • Access State: Open Access