PITUITARY-ADENOMAS - SCREENING FOR G-ALPHA-Q MUTATIONS

Mutant, guanosine triphosphatase-deficient; alpha-subunits of the G pr otein, Gs, gsp ocogene have been discovered in 40% of GH-secreting pit uitary adenomas. Therefore, we hypothesized that a novel G protein cla ss, G alpha q, involved in pituitary signal transduction, might be inv olved in pituitary tumorigenesis. Recombinant mutations of G alpha q r esult in constitutive activation of phospholipase C and have transform ing activity. Therefore, we screened tumor samples from 37 pituitary a denomas for the presence of activating mutations of the G alpha q gene . Importantly, our sample contains 8 FSH and LH adenomas. In the pitui tary gland, FSH and LH are linked to the GnRH-G alpha q signaling casc ade, making these tumors a logical choice for screening for G alpha q mutations. Complementary DNA (cDNA) was synthesized by RT-PCR with G a lpha q specific primers to exclude pseudogene transcripts. Fragments o f G alpha q cDNA-encompassing residues (Arg(183), Gln(209)) were scree ned by single-strand conformation polymorphism and then sequenced in b oth directions. No mutations were detected. We conclude that mutations in these regions of the G alpha q cDNA occur infrequently, if at all, in human pituitary adenomas. Alternative mechanisms underlying pituit ary tumorigenesis should be explored.