title: Six novel MEN1 gene mutations in sporadic parathyroid tumors.
abstract: We report nine mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in sporadic parathyroid adenomas. Six of them have not previously been described: E60X, P32R, 261delA, 934+2T-->G, S443P, and 1593insC. The tissue samples were initially submitted to LOH analysis at 11q13 followed by SSCP screening of LOH-positive samples. Mutations were identified by direct sequencing and subcloning. Three (E60X, P32R, and 261delA) were in exon 2, one (934+2bp) in the splice junction of exon 5, one (S443P) in exon 9, and one (1593insC) in exon 10. The 3 mutations in exon 2 were associated with loss and/or creation of a restriction site. The corresponding germline sequence of the MEN1 gene was normal. Most mutations would likely result in a nonfunctional menin protein, and therefore in the loss of a tumor suppressor protein.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cetani
authors.forename: E
authors.initials: E
authors.lastname: Pardi
authors.forename: A
authors.initials: A
authors.lastname: Giovannetti
authors.forename: P
authors.initials: P
authors.lastname: Cerrai
authors.forename: S
authors.initials: S
authors.lastname: Borsari
authors.forename: E
authors.initials: E
authors.lastname: Vignali
authors.forename: A
authors.initials: A
authors.lastname: Picone
authors.forename: L
authors.initials: L
authors.lastname: Cianferotti
authors.forename: P
authors.initials: P
authors.lastname: Miccoli
authors.forename: A
authors.initials: A
authors.lastname: Pinchera
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
mesh_terms: D000236:Adenoma / Q000235:genetics; D000368:Aged; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D010282:Parathyroid Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D017384:Sequence Deletion / Q000235:genetics
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins