title: Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors.
abstract: We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. cetani@endoc.med.unipi.it.
authors.forename: Filomena
authors.initials: F
authors.lastname: Cetani
authors.forename: Elena
authors.initials: E
authors.lastname: Pardi
authors.forename: Simona
authors.initials: S
authors.lastname: Borsari
authors.forename: Paolo
authors.initials: P
authors.lastname: Viacava
authors.forename: Giada
authors.initials: G
authors.lastname: Dipollina
authors.forename: Luisella
authors.initials: L
authors.lastname: Cianferotti
authors.forename: Elena
authors.initials: E
authors.lastname: Ambrogini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gazzerro
authors.forename: Giacomo
authors.initials: G
authors.lastname: Colussi
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
mesh_terms: D000236:Adenoma / Q000235:genetics; D000328:Adult; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: C454900:CDC73 protein, human; D011506:Proteins; D025521:Tumor Suppressor Proteins