HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours

Background: Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. Methods: Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: f...

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Vydáno v:	Journal of medical genetics Ročník 40; číslo 9; s. 657 - 663
Hlavní autoři:	Howell, V M, Haven, C J, Kahnoski, K, Khoo, S K, Petillo, D, Chen, J, Fleuren, G J, Robinson, B G, Delbridge, L W, Philips, J, Nelson, A E, Krause, U, Hammje, K, Dralle, H, Hoang-Vu, C, Gimm, O, Marsh, D J, Morreau, H, Teh, B T
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BMJ Publishing Group Ltd 01.09.2003 BMJ BMJ Publishing Group LTD BMJ Group
Témata:	Adult Aged Analysis Biological and medical sciences Cancer Chi-Square Distribution Chromosomes, Human, Pair 1 - genetics Development and progression DNA Mutational Analysis DNA, Complementary - chemistry DNA, Complementary - genetics DNA, Neoplasm - chemistry DNA, Neoplasm - genetics Endocrine gland tumors Endocrinopathies familial isolated hyperparathyroidism Family Health Female FIHP Gene mutations Genetic aspects HPT HPT-JT HRPT2 Humans Hyperparathyroidism Hyperparathyroidism - genetics hyperparathyroidism-jaw tumour syndrome Hyperplasia Lithium LOH Loss of Heterozygosity Male Malignant tumors Medical genetics Medical sciences MEN Microsatellite Repeats Middle Aged multiple endocrine neoplasia Mutation Original parathyroid carcinoma Parathyroid Neoplasms - genetics Parathyroid Neoplasms - pathology Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases) Patients Polymorphism, Genetic Proteins - genetics Syndrome Tumor Suppressor Proteins Tumors tumour suppressor Germany Endocrinopathy Human Sporadic Parathyroid diseases Parathyroid tumor Genetics Malignancy Mutation Malignant tumor
ISSN:	0022-2593, 1468-6244, 1468-6244
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Shrnutí:	Background: Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. Methods: Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: five HPT-JT, three FIHP, three MEN 1, one MEN 2A, 25 sporadic adenomas, 17 hyperplastic glands, two lithium associated tumours, and four sporadic carcinomas. Loss of heterozygosity at 1q24-32 was performed on a subset of these tumours. Results:HRPT2 somatic mutations were detected in four of four sporadic parathyroid carcinoma samples, and germline mutations were found in five of five HPT-JT parathyroid tumours (two families) and two parathyroid tumours from one FIHP family. One HPT-JT tumour with germline mutation also harboured a somatic mutation. In total, seven novel and one previously reported mutation were identified. “Two-hits” (double mutations or one mutation and loss of heterozygosity at 1q24-32) affecting HRPT2 were found in two sporadic carcinomas, two HPT-JT-related and two FIHP related tumours. Conclusions: The results in this study support the role of HRPT2 as a tumour suppressor gene in sporadic parathyroid carcinoma, and provide further evidence for HRPT2 as the causative gene in HPT-JT, and a subset of FIHP. In light of the strong association between mutations of HRPT2 and sporadic parathyroid carcinoma demonstrated in this study, it is hypothesised that HRPT2 mutation is an early event that may lead to parathyroid malignancy and suggest intragenic mutation of HRPT2 as a marker of malignant potential in both familial and sporadic parathyroid tumours.
Bibliografie:	istex:4E887A24AC949F263091CD35B9AA080D3F06F499 local:0400657 Correspondence to:  Dr B T Teh  bin.teh@vai.rog, or Dr H Morreau; j-morreau@lumc.nl, or Dr D J Marsh; Debbie_Marsh@med.usyd.edu.au ark:/67375/NVC-QNH2G75Q-V href:jmedgenet-40-657.pdf PMID:12960210 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0022-2593 1468-6244 1468-6244
DOI:	10.1136/jmg.40.9.657