ACTIVATING MUTATIONS OF THE GS ALPHA-GENE IN NONFUNCTIONING PITUITARY-TUMORS

被引:110
作者
TORDJMAN, K
STERN, N
OUAKNINE, G
YOSSIPHOV, Y
RAZON, N
NORDENSKJOLD, M
FRIEDMAN, E
机构
[1] TEL AVIV UNIV, ELIAS SOURASKY MED CTR, SACKLER SCH MED, IL-69978 TEL AVIV, ISRAEL
[2] KAROLINSKA INST, DEPT CLIN GENET, S-10401 STOCKHOLM 60, SWEDEN
关键词
D O I
10.1210/jc.77.3.765
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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(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(i2)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 G(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.
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页码:765 / 769
页数:5
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