Activating mutations of the G[sub s] [alpha]-gene in nonfucntioning pituitary tumors
- Tel-Aviv Univ. Sackler School of Medicine, Tel-Aviv (Israel)
- Karolinska Institute, Stockholm (Sweden)
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, G[sub s][alpha] (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another [alpha]-subunit of a GTP-binding protein, G[sub i2][alpha] (gip mutations) have been described in other endocrine tumors. In this study, the authors examined 21 nonfunctioning pituitary tumors and 4 macro-prolactinomas 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 G[sub s] [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. 27 refs., 3 figs., 1 tab.
- OSTI ID:
- 5017516
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism; (United States), Vol. 77:3; ISSN 0021-972X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PITUITARY GLAND
NEOPLASMS
PROTEINS
GENE MUTATIONS
DNA SEQUENCING
GUANOSINE
AROMATICS
AZAARENES
BODY
DISEASES
ENDOCRINE GLANDS
GLANDS
HETEROCYCLIC COMPOUNDS
MUTATIONS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PURINES
RIBOSIDES
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics