title: GH-secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23-24.
abstract: OBJECTIVE
  The molecular events leading to the development of GH-secreting pituitary tumours remain largely unknown. Gsalpha (GNAS1) mutations are found in 27-43% of sporadic GH-secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4-9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH-secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RIalpha regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) on 17q23-24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH-secreting adenomas in about 10%. We re-evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH-secreting adenomas.
  
  
  METHODS
  We analysed exons 8 and 9 of GNAS1 and all exons and the exon-intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH-secreting pituitary adenomas (30 GH-secreting adenomas, two GH and PRL-secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23-24 with four microsatellite markers and intragenic markers of PRKAR1A.
  
  
  RESULTS
  Seventeen of 32 (53.1%) tumours showed somatic-activating mutations of GNAS1: 16 (53.3%) of 30 GH-secreting adenomas and one of two GH and PRL-secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23-24 were detected in any of the tumours examined.
  
  
  CONCLUSIONS
  We reconfirm the important role of activating mutations of GNAS1 in GH-secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis.
authors.affiliation: Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Tokushima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizusawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002886:Chromosomes, Human, Pair 17; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases