Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.
The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.
Institute of Endocrinology, Elias Sourasky Tel-Aviv Medical Center, Tel-Aviv University Sackler School of Medicine, Israel.
K
K
Tordjman
N
N
Stern
G
G
Ouaknine
Y
Y
Yossiphov
N
N
Razon
M
M
Nordenskjöld
E
E
Friedman
D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003062:Codon; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D019204:GTP-Binding Proteins / Q000235:genetics*; D013006:Growth Hormone / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011388:Prolactin / Q000032:analysis; D015175:Prolactinoma / Q000235:genetics*; D017422:Sequence Analysis, DNA
D003062:Codon; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D019204:GTP-Binding Proteins