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Chae, Kim, Kim, and Chang: Somatic Mutational Analysis of MEN1 and Phenotypic Correlation in Sporadic Parathyroid Tumors
Original Article
Journal of the Korean Surgical Society

Journal of the Korean Surgical Society 2009; 76(1): 15-22.

Published online: 31 January 2009

DOI: https://doi.org/10.4174/jkss.2009.76.1.15

Somatic Mutational Analysis of MEN1 and Phenotypic Correlation in Sporadic Parathyroid Tumors

Young Su Chae, M.D., Hee Jin Kim, M.D.1, Sun Wook Kim, M.D.2, Myung-Chul Chang, M.D.

Department of Surgery, Dankook University College of Medicine, Cheonan, Korea.

1Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.

2Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

changmc@dankook.ac.kr

Received 16 June 2008       Accepted 7 August 2008

Copyright © 2009 The Korean Surgical Society

Abstract

Purpose

MEN1 gene mutation causes multiple endocrine neoplasia type 1. It also suggests that somatic MEN1 gene mutation plays a role in sporadic endocrine tumor. In this study, we examined whether somatic mutations of MEN1 gene are responsible for sporadic parathyroid tumors and correlate with clinical manifestations of parathyroid tumors.

Methods

Somatic mutation of MEN1 gene in the formalin-fixed, paraffin-embedded parathyroid tumor tissue from 8 adenomas, 2 carcinomas and 1 hyperplasia were analyzed by direct sequencing. Clinicopathological parameters were reviewed from medical records and compared with the mutational data.

Results

Eight of eleven (73%) sporadic parathyroid tumors had somatic MEN1 mutations of 14 different types. In the 14 types, 13 were a point mutation which is composed of 8 missense mutations, 2 nonsense mutations and 3 silent mutations. One of 14 types is a frameshift deletion of 27 base pairs in exon 2. Somatic mutation was frequent in the exon 2 and exon 10. Four types of polymorphism were found. There was no correlation between the presence of mutations and clinicopathological phenotype of parathyroid tumors.

Conclusion

This result suggests that somatic mutation of MEN1 gene plays a definite role in sporadic parathyroid tumor formation.

Keywords: Parathyroid, MEN1, Sporadic, Somatic mutation

Figures and Tables

Fig. 1
The agarose gel electrophoresis of exon 2B of MEN1 in case 1, 3, 4, 10 parathyroid tissue. The band of case 3 (arrow) was double.
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Fig. 2
The direct sequencing result of lower part band of exon 2B of MEN1 in case 3 parathyroid tissue. The lower graph was normal wild type and the upper graph was mutated result. The underlined 27bp sequences of normal wild type were deleted.
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Fig. 3
Schematic representation of genomic structure and position of mutations and polymorphisms in the MEN1 gene. The upper part was the mutation and the lower part was the polymorphism. The length of the vertical line indicates the frequency of mutations. The shaded areas of exon 1 and part of exon 2 and 10 are non-translated code.
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Table 1
PCR primers used for MEN1 somatic mutation analysis
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Table 2
Clinicopathological characteristics in sporadic parathyroid tumors
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*U = Uniglandular; †M = Multiglandular; ‡PTH = parathyroid hormone; §ALP = alkaline phosphatase; ∥Sx = symptom; BMD = bone mineral density; **Na = not available.

Table 3
MEN1 gene somatic mutation in sporadic parathyroid tumors
jkss-76-15-i003

*Homo = homozygote; †Hetero = heterozygote; ‡Gln = Glutamine; §Lys = Lysine; ∥Leu = Leucine; Pro = Proline; **Arg = Arginine; ††Cys = Cysteine; ‡‡Gly = Glycine; §§Glu = Glutamic acid; ∥∥Tyr = Tyrosine; ¶¶His = Histidine.

Table 4
Clinicopathological parameters of MEN1 mutation-positive and negative parathyroid tumors
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*ALP = alkaline phosphatase.

Table 5
MEN1 gene somatic polymorphism in sporadic parathyroid tumors
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*Homo = homozygote; †Hetero = heterozygote; ‡Asp = Aspartic acid; §Ala = Alanine; ∥Thr = Threonine.

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