title: Molecular and trophic mechanisms of pituitary tumourigenesis.
abstract: BACKGROUND
  The paradox of pituitary tumours is that persistent growth is so atypical. By definition, all pituitary microadenomas regain complete trophic stability after an initial period of deregulated growth. Unlike tumours in many other organ systems, concern about significant growth of macroadenoma remnants after debulking is minimal. Despite reports of a relatively high prevalence of aneuploidy and clonal skewing in these tumours, prolonged efforts to implicate classical proto-oncogene activation and tumour suppressor mutations have been of limited success. No histological or molecular markers reliably predict behaviour. To date, the number of molecular genetic factors unequivocally linked to pituitary tumours can be counted on the fingers of one hand: (1) GNAS1 activation in acromegaly; (2) the MENIN and p27Kip1 (CDKN1B) mutations associated with multiple endocrine neoplasia type 1; (3) mutations of PRKA1RA with loss of 17q22-24 in Carney complex, and (4) aryl hydrocarbon receptor interacting protein gene mutations in 15% of familial isolated pituitary adenomas and 50% of familial isolated acromegaly. Together, these account for only a small proportion (<5%) of sporadic pituitary macroadenomas.
  
  
  CONCLUSIONS
  In most instances, we still do not know what causes quantitative aberrations in trophic behaviour.
authors.affiliation: Bristol University and United Bristol Healthcare Trust, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. a.levy@bris.ac.uk
authors.forename: Andy
authors.initials: A
authors.lastname: Levy
mesh_terms: D000172:Acromegaly / Q000235:genetics; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D056733:Carney Complex / Q000235:genetics; D002864:Chromogranins; D044127:Epigenesis, Genetic; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D010902:Pituitary Gland / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas
chemical_list: D002864:Chromogranins; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C103265:aryl hydrocarbon receptor-interacting protein; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs