title: MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism.
abstract: 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.
  
  
  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), β-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.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal.
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Alvelos
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.forename: Elsa
authors.initials: E
authors.lastname: Fonseca
authors.forename: Eva
authors.initials: E
authors.lastname: Barbosa
authors.forename: José
authors.initials: J
authors.lastname: Teixeira-Gomes
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012189:Retrospective Studies
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human