Pituitary adenomas: Screening for Gαq mutations

Abstract

Mutant, guanosine triphosphatase-deficient, α-subunits of the G protein, Gs,gsp ocogene have been discovered in 40% of GH-secreting pituitary adenomas. Therefore, we hypothesized that a novel G protein class, Gαq, involved in pituitary signal transduction, might be involved in pituitary tumorigenesis. Recombinant mutations of Gαq result in constitutive activation of phospholipase C and have transforming activity. Therefore, we screened tumor samples from 37 pituitary adenomas for the presence of activating mutations of the Gαq gene. Importantly, our sample contains 8 FSH and LH adenomas. In the pituitary gland, FSH and LH are linked to the GnRH- Gαq signaling cascade, making these tumors a logical choice for screening for Gαq mutations. Complementary DNA (cDNA) was synthesized by RT-PCR with Gαq specific primers to exclude pseudogene transcripts. Fragments of Gαq cDNA-encompassing residues (Arg183, Gln209) were screened by single- strand conformation polymorphism and then sequenced in both directions. No mutations were detected. We conclude that mutations in these regions of the Gαq cDNA occur infrequently, if at all, in human pituitary adenomas. Alternative mechanisms underlying pituitary tumorigenesis should be explored.