title: Genomic sequence analysis of a key residue (Arg183) in human G alpha q in invasive non-functional pituitary adenomas.
abstract: OBJECTIVE
  With isolated exceptions the only oncogene significantly associated with pituitary tumours is a constitutively active Gs protein (G alpha s). The recent cloning of the cDNA of human G alpha q has facilitated the study of this activator of the phospholipase C beta/Ca2+/ protein kinase C pathway. Since, with isolated exceptions, non-functional tumours are responsive in vitro to TRH and GnRH which activate Gq, we have investigated the genomic sequence of G alpha q, in non-functional (NF) invasive pituitary adenomas, at a residue corresponding to the one most frequently mutated in G alpha s.
  
  
  METHODS
  We studied 27 invasive NF pituitary tumours by direct sequencing of DNA derived from archival slide extracted tumour cells. Primers were designed to encompass Arg183 (corresponding to Arg201 of G alpha s) which when mutated has been shown to have oncogenic potential when transfected into cultural rat fibroblasts. In a previous study we have described allelic loss at tumour suppressor gene loci (TSG) in 7 of these 27 tumours.
  
  
  RESULTS
  We successfully amplified genomic DNA with primers designed from the cDNA sequence of G alpha q with specific exclusion of a processed pseudogene. No mutations were found at Arg183, in either the tumours showing allelic losses at specific TSG loci, or in the 20 remaining tumours in which we found no losses at the TSG loci investigated.
  
  
  CONCLUSIONS
  Mutations at this key residue in G alpha q occur infrequently, if at all, in invasive non-functional pituitary tumours. However we cannot exclude the possibility of mutation(s) at the other key residue of G alpha q, Gin209, implicated in GTP hydrolysis, or in other components of this pathway.
authors.affiliation: Centre for Cell and Molecular Medicine, School of Post Graduate Medicine, University of Keele, Stoke-on-Trent, UK.
authors.forename: W E
authors.initials: WE
authors.lastname: Farrell
authors.forename: J A
authors.initials: JA
authors.lastname: Talbot
authors.forename: E J
authors.initials: EJ
authors.lastname: Bicknell
authors.forename: D
authors.initials: D
authors.lastname: Simpson
authors.forename: R N
authors.initials: RN
authors.lastname: Clayton
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000235:genetics*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins