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Multiple endocrine neoplasia type 1: clinical correlates of MEN1 gene methylation


De Paoli-Iseppi, R and Prentice, L and Marthick, JR and Thomson, R and Holloway, AF and Dickinson, JL and Burgess, J, Multiple endocrine neoplasia type 1: clinical correlates of MEN1 gene methylation, Pathology, 50, (6) pp. 622-628. ISSN 0031-3025 (2018) [Refereed Article]

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Copyright 2018 Royal College of Pathologists of Australasia. This is a non-final version of an article published in final form in Pathology, 50(6), 2018

DOI: doi:10.1016/j.pathol.2018.05.006


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 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.

Item Details

Item Type:Refereed Article
Keywords:epigenetics, multiple endocrine neoplasia type 1, methylation, MEN 1, parathyroid, familial
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Medical genetics (excl. cancer genetics)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:De Paoli-Iseppi, R (Mr Ricardo De Paoli-Iseppi)
UTAS Author:Prentice, L (Dr Louise Prentice)
UTAS Author:Marthick, JR (Mr James Marthick)
UTAS Author:Thomson, R (Dr Russell Thomson)
UTAS Author:Holloway, AF (Professor Adele Holloway)
UTAS Author:Dickinson, JL (Professor Joanne Dickinson)
UTAS Author:Burgess, J (Professor John Burgess)
ID Code:127326
Year Published:2018
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-07-21
Last Modified:2022-08-29
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