PMID- 26732163
OWN - NLM
STAT- MEDLINE
DCOM- 20170105
LR  - 20180409
IS  - 2520-8721 (Electronic)
IS  - 1109-3099 (Linking)
VI  - 15
IP  - 1
DP  - 2016 Jan-Mar
TI  - Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation 
      in a family with atypical tumor phenotype.
PG  - 113-7
LID - 10.14310/horm.2002.1626 [doi]
AB  - 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.
FAU - Perakakis, Nikolaos
AU  - Perakakis N
AD  - Division of Endocrinology and Diabetology, Department of Internal Medicine II, 
      University Hospital of Freiburg, Freiburg, Germany.
FAU - Flohr, Felix
AU  - Flohr F
AD  - Department of Internal Medicine I, St. Vincentius-Hospital, Karlsruhe, Germany.
FAU - Kayser, Gian
AU  - Kayser G
AD  - Department of Pathology, Institute of Surgical Pathology, University Hospital of 
      Freiburg, Freiburg, Germany.
FAU - Thomusch, Oliver
AU  - Thomusch O
AD  - Division of Endocrine Surgery, Department of General and Visceral Surgery, 
      University Hospital of Freiburg, Germany.
FAU - Parsons, Lydia
AU  - Parsons L
AD  - Division of Endocrinology and Diabetology, Department of Internal Medicine II, 
      University Hospital of Freiburg, Freiburg, Germany,School of Biosciences, Cardiff 
      University, Cardiff, United Kingdom.
FAU - Billmann, Franck
AU  - Billmann F
AD  - Division of Endocrine Surgery, Department of General and Visceral Surgery, 
      University Hospital of Freiburg, Germany.
FAU - von Dobschuetz, Ernst
AU  - von Dobschuetz E
AD  - Division of Endocrine Surgery Hospital Reinbek St. Adolf-Stift Reinbek, Germany.
FAU - Rondot, Susanne
AU  - Rondot S
AD  - Endocrine Practice and Molecular Laboratory, Heidelberg, Germany.
FAU - Seufert, Jochen
AU  - Seufert J
AD  - Division of Endocrinology and Diabetology, Department of Internal Medicine II, 
      University Hospital of Freiburg, Freiburg, Germany.
FAU - Laubner, Katharina
AU  - Laubner K
AD  - Division of Endocrinology and Diabetology, Department of Internal Medicine II, 
      University Hospital of Freiburg, Freiburg, Germany.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Switzerland
TA  - Hormones (Athens)
JT  - Hormones (Athens, Greece)
JID - 101142469
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Aged
MH  - Gene Expression Regulation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation, Missense
MH  - Pedigree
MH  - Prostatic Neoplasms/genetics/metabolism
MH  - Proto-Oncogene Proteins/genetics/*metabolism
EDAT- 2016/01/07 06:00
MHDA- 2017/01/06 06:00
CRDT- 2016/01/07 06:00
PHST- 2015/05/28 00:00 [received]
PHST- 2015/09/09 00:00 [accepted]
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2017/01/06 06:00 [medline]
AID - 10.14310/horm.2002.1626 [doi]
PST - ppublish
SO  - Hormones (Athens). 2016 Jan-Mar;15(1):113-7. doi: 10.14310/horm.2002.1626.