title: Identification of somatic mutations of the MEN1 gene in sporadic endocrine tumours.
abstract: Endocrine tumours of the pancreas, anterior pituitary or parathyroids arise either sporadically in the general population, or as a part of inherited syndromes such as multiple endocrine neoplasia type 1 (MEN 1). The mechanisms responsible for the development of sporadic endocrine lesions are not well understood, although loss of heterozygosity (LOH) of the MEN1 locus on chromosome 11q13 and somatic mutation of the MEN1 gene have been frequently associated with the development of MEN 1-type sporadic endocrine lesions. To further investigate the role of the MEN1 gene in sporadic endocrine tumorigenesis, we analysed DNA from 14 primary parathyroid lesions, 8 anterior pituitary tumours and 3 pancreatic tumours for the presence of somatic MEN1 gene mutations and LOH of seven microsatellite markers flanking the MEN1 locus. In addition, we similarly analysed 8 secondary parathyroid lesions which arose in patients with chronic renal failure. None of the patients studied had a family history of MEN 1. Three primary parathyroid lesions and one pancreatic tumour (glucagonoma) were found to have lost one allele at the MEN1 locus. Somatic mutations were identified by SSCP and sequence analysis in one of these parathyroid lesions (P320L) and in the glucagonoma (E179V). These results support previous findings that inactivation of the MEN1 tumour suppressor gene contributes to the development of sporadic MEN 1-type endocrine lesions but is not associated with the development of parathyroid hyperplasia seen in some renal failure patients.
authors.affiliation: Queensland Cancer Fund Research Unit, Joint Experimental Oncology Programme of the Queensland Institute of Medical Research and the University of Queensland, Herston, QLD 4029, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Bergman
authors.forename: C
authors.initials: C
authors.lastname: Boothroyd
authors.forename: J
authors.initials: J
authors.lastname: Palmer
authors.forename: S
authors.initials: S
authors.lastname: Grimmond
authors.forename: M
authors.initials: M
authors.lastname: Walters
authors.forename: B
authors.initials: B
authors.lastname: Teh
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: L
authors.initials: L
authors.lastname: Hartley
authors.forename: N
authors.initials: N
authors.lastname: Hayward
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D016147:Genes, Tumor Suppressor; D006801:Humans; D016030:Kidney Transplantation; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000601:surgery; D010279:Parathyroid Diseases / Q000235:genetics / Q000601:surgery; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000601:surgery; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000601:surgery; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins