Pituitary adenomas: screening for G alpha q mutations.
Mutant, guanosine triphosphatase-deficient, alpha-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, G alpha q, involved in pituitary signal transduction, might be involved in pituitary tumorigenesis. Recombinant mutations of G alpha q 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 G alpha q gene. Importantly, our sample contains 8 FSH and LH adenomas. In the pituitary gland, FSH and LH are linked to the GnRH-G alpha q signaling cascade, making these tumors a logical choice for screening for G alpha q mutations. Complementary DNA (cDNA) was synthesized by RT-PCR with G alpha q specific primers to exclude pseudogene transcripts. Fragments of G alpha q 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 G alpha q cDNA occur infrequently, if at all, in human pituitary adenomas. Alternative mechanisms underlying pituitary tumorigenesis should be explored.
Oyesiku
N M
NM
Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA. noyesik@emory.edu
Evans
C O
CO
Brown
M R
MR
Blevins
L S
LS
Tindall
G T
GT
Parks
J S
JS
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014158:Transcription, Genetic
D018076:DNA, Complementary; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins