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Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain.
J Clin Endocrinol Metab. 2014 Nov; 99(11):E2387-91.JC

Abstract

CONTEXT

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.

OBJECTIVE

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.

DESIGN

This was a retrospective analysis of a prospectively collected cohort of 71 genetically confirmed MEN1 patients at a tertiary referral center.

MAIN OUTCOME MEASURES

Analysis of patients' characteristics and clinical phenotype of pNENs regarding the mutation type and its location in Menin interacting domains was measured.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Departments of Visceral, Thoracic, and Vascular Surgery (D.K.B., E.P.S., M.A., R.K., B.C., C.L.L., V.F., J.W.) and Gastroenterology (P.H.K.), Division of Endocrinology and Diabetology, University Hospital Giessen and Marburg, Campus Marburg, 35041 Marburg, Germany.No 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)

Journal Article

Language

eng

PubMed ID

25210877

Citation

Bartsch, Detlef K., et al. "Higher Risk of Aggressive Pancreatic Neuroendocrine Tumors in MEN1 Patients With MEN1 Mutations Affecting the CHES1 Interacting MENIN Domain." The Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 11, 2014, pp. E2387-91.
Bartsch DK, Slater EP, Albers M, et al. Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain. J Clin Endocrinol Metab. 2014;99(11):E2387-91.
Bartsch, D. K., Slater, E. P., Albers, M., Knoop, R., Chaloupka, B., Lopez, C. L., Fendrich, V., Kann, P. H., & Waldmann, J. (2014). Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain. The Journal of Clinical Endocrinology and Metabolism, 99(11), E2387-91. https://doi.org/10.1210/jc.2013-4432
Bartsch DK, et al. Higher Risk of Aggressive Pancreatic Neuroendocrine Tumors in MEN1 Patients With MEN1 Mutations Affecting the CHES1 Interacting MENIN Domain. J Clin Endocrinol Metab. 2014;99(11):E2387-91. PubMed PMID: 25210877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain. AU - Bartsch,Detlef K, AU - Slater,Emily P, AU - Albers,Max, AU - Knoop,Richard, AU - Chaloupka,Brunhilde, AU - Lopez,Caroline L, AU - Fendrich,Volker, AU - Kann,Peter H, AU - Waldmann,Jens, Y1 - 2014/09/11/ PY - 2014/9/12/entrez PY - 2014/9/12/pubmed PY - 2015/1/17/medline SP - E2387 EP - 91 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 99 IS - 11 N2 - CONTEXT: 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. OBJECTIVE: 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. DESIGN: This was a retrospective analysis of a prospectively collected cohort of 71 genetically confirmed MEN1 patients at a tertiary referral center. MAIN OUTCOME MEASURES: Analysis of patients' characteristics and clinical phenotype of pNENs regarding the mutation type and its location in Menin interacting domains was measured. RESULTS: 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. CONCLUSIONS: 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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/25210877/Higher_risk_of_aggressive_pancreatic_neuroendocrine_tumors_in_MEN1_patients_with_MEN1_mutations_affecting_the_CHES1_interacting_MENIN_domain_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2013-4432 DB - PRIME DP - Unbound Medicine ER -