title: Molecular pathogenesis of pituitary tumours.
abstract: Human pituitary tumours account for 10% of intracranial neoplasms. These tumours are usually sporadic and benign; malignant change and metastasis are extremely rare events. Autosomal dominant inheritance of MEN 1 accounts for a minority of pituitary tumours. Pituitary tumours have been found to be monoclonal in several studies. This would suggest that an intrinsic genetic pituitary defect is pivotal in the pathogenesis of these tumours. However, this concept does not exclude a role for the hypothalamus in the genesis of pituitary tumours; the trophic function of several hypothalamic peptides could promote initiation of the genetic event or facilitate a sequence of events leading to clonal expansion of the transformed cell. There has been modest progress made in the elucidation of the intrinsic genetic pituitary cell abnormalities that underlie pituitary tumorigenesis. A mutant alpha subunit of the Gs gene, designated gsp, which results in constitutive activation of adenylyl cylcase has been described in a subset of GH cell adenomas. Loss of genetic material on chromosome 11q13, the locus of the MEN 1 gene, is found in under 20% of pituitary adenomas, suggesting that inactivation of a tumour suppressor gene at this locus may be significant in the tumorigenic process. H-ras point mutations have been described in distant metastatic pituitary tumour secondaries. The genetic abnormalities described occur in only a small subset of pituitary tumours, indicating that the more significant tumour promoting genes are still to be discovered.
authors.affiliation: Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center-UCLA School of Medicine 90048-1865, USA.
authors.forename: V
authors.initials: V
authors.lastname: Herman-Bonert
authors.forename: J A
authors.initials: JA
authors.lastname: Fagin
mesh_terms: D000236:Adenoma / Q000209:etiology* / Q000235:genetics; D000818:Animals; D016147:Genes, Tumor Suppressor; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D009857:Oncogenes; D010902:Pituitary Gland / Q000378:metabolism / Q000502:physiology; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D006728:Hormones