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Hormones

, Volume 15, Issue 1, pp 113–117 | Cite as

Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype

  • Nikolaos Perakakis
  • Felix Flohr
  • Gian Kayser
  • Oliver Thomusch
  • Lydia Parsons
  • Franck Billmann
  • Ernst von Dobschuetz
  • Susanne Rondot
  • Jochen Seufert
  • Katharina Laubner
Case report

Abstract

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant hereditary disorder associated with the development of endocrine tumors due to reduced expression of the tumor suppressor protein menin. Recent studies indicate a general role of menin in carcinogenesis, affecting the prevalence and clinical course of common non-endocrine tumors such as breast cancer, hepatocellular carcinoma and melanoma. Here we report a new germline missense mutation of Men1 in a German family with atypical tumor phenotype over three generations. Based on the type of mutation, we discuss possible changes in menin function leading to atypical tumorigenesis and present the clinical significance of such findings. CASE PRESENTATION: A German family with a history of primary hyperparathyroidism presented to our Hospital for further evaluation. Members of the family demonstrated many different atypical tumors, such as renal cell carcinoma, papillary thyroid cancer and prostate cancer. DNA sequencing from peripheral blood revealed a novel mutation: Ser38Cys [TCC>TGC] in exon 2, codon 38 of Men1. This novel mutation is located in a region of menin which is responsible for interactions with the transcription factor JunD. This factor has recently been associated with prostate cancer. DNA sequencing of two of the atypical tumors (prostate cancer, papillary thyroid cancer) did not reveal a loss of heterozygosity, indicating an impact on menin expression and function in the heterozygous state, in line with results in +/−Men1 mutant mice developing prostate cancer. CONCLUSION: The results and clinical course of disease in this case indicate the potential role of menin in the development of non-endocrine or atypical-endocrine tumors in MEN1 patients. Further investigations are needed to clarify both the general role of menin and the importance of specific mutations in carcinogenesis. Nevertheless, in families with uncommon manifestations of the syndrome early diagnostic adjustments should be considered.

Key words

Atypical tumors MEN1 New mutation Prostate cancer 

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Copyright information

© Hellenic Endocrine Society 2016

Authors and Affiliations

  • Nikolaos Perakakis
    • 1
  • Felix Flohr
    • 2
  • Gian Kayser
    • 3
  • Oliver Thomusch
    • 4
  • Lydia Parsons
    • 1
    • 5
  • Franck Billmann
    • 4
  • Ernst von Dobschuetz
    • 6
  • Susanne Rondot
    • 7
  • Jochen Seufert
    • 1
  • Katharina Laubner
    • 1
  1. 1.Division of Endocrinology and Diabetology, Department of Internal Medicine IIUniversity Hospital of FreiburgFreiburgGermany
  2. 2.Department of Internal Medicine ISt. Vincentius-HospitalKarlsruheGermany
  3. 3.Department of Pathology, Institute of Surgical PathologyUniversity Hospital of FreiburgFreiburgGermany
  4. 4.Division of Endocrine Surgery, Department of General and Visceral SurgeryUniversity Hospital of FreiburgFreiburgGermany
  5. 5.School of BiosciencesCardiff UniversityCardiffUK
  6. 6.Division of Endocrine SurgeryHospital Reinbek St. Adolf-Stift ReinbekReinbekGermany
  7. 7.Endocrine Practice and Molecular LaboratoryHeidelbergGermany

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