PMID- 30149991
OWN - NLM
STAT- MEDLINE
DCOM- 20181107
LR  - 20181107
IS  - 1465-3931 (Electronic)
IS  - 0031-3025 (Linking)
VI  - 50
IP  - 6
DP  - 2018 Oct
TI  - Multiple endocrine neoplasia type 1: clinical correlates of MEN1 gene 
      methylation.
PG  - 622-628
LID - S0031-3025(16)40563-5 [pii]
LID - 10.1016/j.pathol.2018.05.006 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN 1) has marked severity variation between 
      individuals with the same mutation. To investigate any relationship between 
      promoter methylation and clinical features, blood and tissue samples were 
      collected from 16 members of the Tasman 1 MEN 1 kindred carrying a common splice 
      site mutation and 7 patients with sporadic MEN 1. Methylation at 39 CpGs in the 
      MEN1 promoter were assessed in formalin fixed, paraffin embedded parathyroid 
      tissue. Clinical disease severity markers included age at first parathyroid 
      operation, parathyroid hormone level and corrected serum calcium levels. Six 
      patients with sporadic hyperparathyroidism were used for comparison. Minimal 
      methylation was observed in all patients across CpG sites 1-23. In contrast, 
      hypermethylation was observed at CpG sites 24-31 in MEN 1 patients, a pattern not 
      observed in patients with non-MEN 1 parathyroid disease. Mean methylation at 
      sites 24-31 was significantly correlated with age at first parathyroid operation 
      (r = 0.652, p = 0.041). A permutation test, utilising the mean correlation 
      coefficient (r = -0.401) revealed a possible association between relative PHPT 
      severity and methylation score for each significant CpG site (p < 0.103). This 
      novel study reveals evidence supporting a possible association between altered 
      MEN1 promoter methylation and clinical severity of disease.
CI  - Copyright (c) 2018 Royal College of Pathologists of Australasia. Published by 
      Elsevier B.V. All rights reserved.
FAU - De Paoli-Iseppi, Ricardo
AU  - De Paoli-Iseppi R
AD  - Cancer Genetics and Immunology, Menzies Institute for Medical Research, 
      University of Tasmania, Hobart, Tas, Australia.
FAU - Prentice, Louise
AU  - Prentice L
AD  - School of Medicine, University of Tasmania, Hobart, Tas, Australia; Royal Hobart 
      Hospital, Hobart, Tas, Australia.
FAU - Marthick, James R
AU  - Marthick JR
AD  - Cancer Genetics and Immunology, Menzies Institute for Medical Research, 
      University of Tasmania, Hobart, Tas, Australia.
FAU - Thomson, Russell
AU  - Thomson R
AD  - Cancer Genetics and Immunology, Menzies Institute for Medical Research, 
      University of Tasmania, Hobart, Tas, Australia.
FAU - Holloway, Adele F
AU  - Holloway AF
AD  - School of Medicine, University of Tasmania, Hobart, Tas, Australia.
FAU - Dickinson, Joanne L
AU  - Dickinson JL
AD  - Cancer Genetics and Immunology, Menzies Institute for Medical Research, 
      University of Tasmania, Hobart, Tas, Australia. Electronic address: 
      Jo.Dickinson@utas.edu.au.
FAU - Burgess, John
AU  - Burgess J
AD  - School of Medicine, University of Tasmania, Hobart, Tas, Australia; Royal Hobart 
      Hospital, Hobart, Tas, Australia.
LA  - eng
PT  - Journal Article
DEP - 20180824
PL  - England
TA  - Pathology
JT  - Pathology
JID - 0175411
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - DNA Methylation/*genetics
MH  - Female
MH  - Humans
MH  - Hyperparathyroidism/genetics
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Young Adult
OTO - NOTNLM
OT  - MEN 1
OT  - Methylation
OT  - familial
OT  - parathyroid
EDAT- 2018/08/29 06:00
MHDA- 2018/11/08 06:00
CRDT- 2018/08/29 06:00
PHST- 2016/12/20 00:00 [received]
PHST- 2018/05/18 00:00 [revised]
PHST- 2018/05/22 00:00 [accepted]
PHST- 2018/08/29 06:00 [pubmed]
PHST- 2018/11/08 06:00 [medline]
PHST- 2018/08/29 06:00 [entrez]
AID - S0031-3025(16)40563-5 [pii]
AID - 10.1016/j.pathol.2018.05.006 [doi]
PST - ppublish
SO  - Pathology. 2018 Oct;50(6):622-628. doi: 10.1016/j.pathol.2018.05.006. Epub 2018 
      Aug 24.