title: Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1.
abstract: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centromerically by PYGM and telomerically by D11S1783 defined by combined meiotic and tumour deletion mapping studies. Two candidate genes, ZFM1 and PPP2R5B, from this region have been previously excluded, and in order to identify additional candidate genes we used a BAC to isolate cDNAs from a bovine parathyroid cDNA library by direct selection. One of the novel genes that we identified, SCG2, proved to be identical to the recently published MEN1 gene, which is likely to be a tumour suppressor gene. The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also being present in the pancreas and thymus. Mutational analysis of SCG2 in 10 unrelated MEN1 families identified one polymorphism and nine different heterozygous mutations (one missense, four non-sense, one insertional and three deletional frameshifts) that segregated with the disease, hence providing an independent confirmation for the identification of the MEN1 gene.
authors.affiliation: Laboratory for Molecular Oncology and Flanders Interuniversity Institute for Biotechnology, Center for Human Genetics, KU Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Lemmens
authors.forename: W J
authors.initials: WJ
authors.lastname: Van de Ven
authors.forename: K
authors.initials: K
authors.lastname: Kas
authors.forename: C X
authors.initials: CX
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Giraud
authors.forename: V
authors.initials: V
authors.lastname: Wautot
authors.forename: N
authors.initials: N
authors.lastname: Buisson
authors.forename: K
authors.initials: K
authors.lastname: De Witte
authors.forename: J
authors.initials: J
authors.lastname: Salandre
authors.forename: G
authors.initials: G
authors.lastname: Lenoir
authors.forename: M
authors.initials: M
authors.lastname: Pugeat
authors.forename: A
authors.initials: A
authors.lastname: Calender
authors.forename: F
authors.initials: F
authors.lastname: Parente
authors.forename: D
authors.initials: D
authors.lastname: Quincey
authors.forename: P
authors.initials: P
authors.lastname: Gaudray
authors.forename: M J
authors.initials: MJ
authors.lastname: De Wit
authors.forename: C J
authors.initials: CJ
authors.lastname: Lips
authors.forename: J W
authors.initials: JW
authors.lastname: Höppener
authors.forename: S
authors.initials: S
authors.lastname: Khodaei
authors.forename: A L
authors.initials: AL
authors.lastname: Grant
authors.forename: G
authors.initials: G
authors.lastname: Weber
authors.forename: S
authors.initials: S
authors.lastname: Kytölä
authors.forename: B T
authors.initials: BT
authors.lastname: Teh
authors.forename: F
authors.initials: F
authors.lastname: Farnebo
authors.forename: R V
authors.initials: RV
authors.lastname: Thakker
mesh_terms: D000818:Animals; D002417:Cattle; D002876:Chromosomes, Bacterial; D003001:Cloning, Molecular; D003360:Cosmids; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005260:Female; D015723:Gene Library; D006801:Humans; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins
chemical_list: D018076:DNA, Complementary; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins