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

Abstract

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