Non-functioning pituitary adenomas infrequently harbor G-protein gene mutations

J Endocrinol Invest. 2008 Nov;31(11):946-9. doi: 10.1007/BF03345630.

Abstract

Background: Mutations of the genes encoding the alpha subunit of the stimulatory G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes, respectively) have been described in various endocrine neoplasias, including pituitary tumors.

Aim: To search for mutations of GNAS1 and GNAI2 in a continuous series of non-functioning pituitary adenoma (NFPA) patients neurosurgically treated.

Subjects and methods: The surgical samples of 22 patients who have been defined and characterized on a clinical, biochemical, histological, and immunohistochemical point of view have been processed for investigating the presence of the above mutations by PCR amplification of the hot spots exons 8 and 9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover, the promoter region of GNAI2, in order to assess the prevalence of single nucleotide polymorphisms (SNP), was investigated in the same series.

Results: A CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found, but no mutation of GNAI2A was demonstrated.

Conclusions: This finding suggests and confirms that G-protein mutations are rare and not crucial in NFPA development. Additionally, we found a silent SNP at codon 318 in the promoter of the Gi2alpha gene in one out of the 22 NFPA.

MeSH terms

  • Adenoma, Acidophil / genetics*
  • Adenoma, Chromophobe / genetics*
  • Adult
  • Aged
  • Chromogranins
  • Codon / genetics
  • Exons
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Pituitary Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Repressor Proteins

Substances

  • Chromogranins
  • Codon
  • Intracellular Signaling Peptides and Proteins
  • Repressor Proteins
  • URI1 protein, human
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs