title: Tumour suppressor genes in the pathogenesis of human pituitary tumours.
abstract: Abnormal cell proliferation is controlled by opposing actions of oncogene products (stimulatory) and tumour suppressor gene (TSG) products (inhibitory). The former are dominantly acting, i.e. only one copy needed for tumorigenesis, whilst for TSG both copies of the gene must be inactivated so these are recessive at a cellular level. For anterior pituitary tumours only one oncogene (Gsp) has been identified in a variable proportion (4-40%) of a single tumour subtype (somatotrophinomas). Contrariwise, allelic deletion studies, using a PCR-based microsatellite polymorphism analysis of DNA extracted from archival specimens, have shown significant loss of heterozygosity in 20-40% of all tumour subtypes at the locus of the putative MEN-1 gene (chr. 11q13); the retinoblastoma gene (chr. 13q 12-14), and 10q26. Moreover, these DNA microdeletions were concentrated in radiologically invasive tumours compared to noninvasive tumours (modified Hardy gdes 3 and 4 vs. 1 + 2). In addition, 50% of Cushing's adenomas showed presence of p53 immunopositivity, though no point mutations in exons 4-9 were found, by SSCP analysis, to account for this. These studies show that analysis of TSGs in pituitary adenomas may provide clues to their pathogenesis, and more importantly relate to clinical behaviour of the tumour, and hence aid decisions regarding management.
authors.affiliation: Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, Stoke-on-Trent, UK.
authors.forename: R N
authors.initials: RN
authors.lastname: Clayton
authors.forename: M
authors.initials: M
authors.lastname: Boggild
authors.forename: A S
authors.initials: AS
authors.lastname: Bates
authors.forename: J
authors.initials: J
authors.lastname: Bicknell
authors.forename: D
authors.initials: D
authors.lastname: Simpson
authors.forename: W
authors.initials: W
authors.lastname: Farrell
mesh_terms: D002455:Cell Division; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D009857:Oncogenes; D010911:Pituitary Neoplasms / Q000235:genetics*