MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Maria Ines Alvelos (Autor) Outra; Joao Vinagre (Autor) Outra; Elsa Fonseca (Autor) Outra; Eva Barbosa (Autor) Outra; Jose Teixeira Gomes (Autor) Outra; Manuel Sobrinho Simoes (Autor) FMUP; Paula Soares (Autor) FMUP

Revista

Título: European Journal of Endocrinology

Vol. 168

Páginas: 119-128

ISSN: 0804-4643

Editora: BioScientifica Ltd.

Indexação

ISI Web of Knowledge - 27 Citações

Scopus - 29 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-002-0MS

DOI: 10.1530/eje-12-0327

Abstract (EN): Objective: Primary hyperparathyroidism (pHPT) is characterised by an inappropriate over production of parathyroid hormone and it is the most frequent pathological condition of the parathyroid glands. A minority of the cases belong to familial forms, but most of them are sporadic. The genetic alterations underlying the sporadic forms of pHPT remain poorly understood. The main goal of our study is to perform the molecular characterisation of a series of sporadic pHPT cases. Design and methods: We have studied matched blood and tumour from 24 patients with pHPT, who went to a medical appointment in Hospital Pedro Hispano. Informed consent was obtained from all individuals. The MEN1, RET and CDKN1B molecular study was carried out in the germline DNA by PCR/SSCP and direct sequencing. Parathyroid tumours were further analysed by the same methods for MEN1, CDKN1B and CTNNB1 genetic alterations. The multiplex ligation-dependent probe amplification technique enabled the evaluation of MEN1 gene deletions. Protein expression for menin, cyclin D1, parafibromin, p27(Kip1), beta-catenin and Ki-67 was conducted by immunohistochemistry. Results: The study of parathyroid tumours detected two somatic MEN1 mutations (c.249_252delGTCT and c.115_163del49bp) and revealed the presence of MEN1 intragenic deletions in 54% (13/24) of the tumours. In RET and CDKN1B genes only previously described, non-pathogenic variants were found. Cyclin D1 protein was overexpressed in 13% (3/24) of tumours. Conclusions: These results suggest that MEN1 alterations, remarkably intragenic deletions, may represent the most prevalent genetic alteration in sporadic parathyroid tumours. European Journal of Endocrinology 168 119-128

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10