title: Aryl hydrocarbon receptor interacting protein (AIP) mutations occur rarely in sporadic parathyroid adenomas.
abstract: BACKGROUND
  The molecular pathogenesis of primary hyperparathyroidism is still largely unknown. The aryl hydrocarbon receptor interacting protein (AIP) gene has a major role in the pathogenesis of familial isolated pituitary adenoma.
  
  
  OBJECTIVE
  We evaluated the involvement of the AIP gene in sporadic parathyroid adenomas.
  
  
  METHODS
  We performed direct sequencing and multiplex ligation-dependent probe amplification analyses of the AIP gene in a large series of sporadic parathyroid adenomas. Loss of heterozygosity (LOH) at the AIP locus was studied, and aryl hydrocarbon receptor interacting protein immunostaining was also performed. In addition, alterations in the MEN1 gene were studied.
  
  
  RESULTS
  A somatic AIP mutation, substitution of arginine with glutamine at codon 304 (R304Q), was identified in 2 of 132 tumors. The mutation was germline in both cases despite the nonfamilial presentation. Heterozygous AIP large deletions were detected in 29 cases including 1 of the 2 mutated tumors, confirming a biallelic inactivation of the AIP gene. The AIP-mutated tumor with LOH showed decreased AIP immunostaining compared with normal parathyroid. LOH at the MEN1 locus, which often shared LOH at the AIP locus, was found in one third of tumors. Somatic MEN1 mutations were found in the 1 of the 2 AIP-mutated tumors and in 22 parathyroid adenomas. In addition, multiplex ligation-dependent probe amplification analysis revealed 1 large deletion of the MEN1 gene in 1 patient.
  
  
  CONCLUSIONS
  The AIP gene is rarely involved in parathyroid adenomas, but the germline nature of the mutations suggests that it might predispose to primary hyperparathyroidism. MEN1 gene alterations occur in a substantial proportion of sporadic parathyroid adenomas.
authors: Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy.
authors: Elena
authors: E
authors: Pardi
authors: Claudio
authors: C
authors: Marcocci
authors: Simona
authors: S
authors: Borsari
authors: Federica
authors: F
authors: Saponaro
authors: Liborio
authors: L
authors: Torregrossa
authors: Mariella
authors: M
authors: Tancredi
authors: Benedetta
authors: B
authors: Raspini
authors: Fulvio
authors: F
authors: Basolo
authors: Filomena
authors: F
authors: Cetani
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007558:Italy; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C103265:aryl hydrocarbon receptor-interacting protein