Tordjman K, Stern N, Ouaknine G, Yossiphov Y, Razon N, Nordenskjöld M, Friedman E
Institute of Endocrinology, Elias Sourasky Tel-Aviv Medical Center, Tel-Aviv University Sackler School of Medicine, Israel.
J Clin Endocrinol Metab. 1993 Sep;77(3):765-9. doi: 10.1210/jcem.77.3.8396579.
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.
大多数垂体肿瘤起源于单克隆；然而，其形成的分子基础却知之甚少。在约三分之一的生长激素分泌性肿瘤中发现了GTP结合蛋白Gsα亚基的体细胞突变（gsp癌基因）。在其他内分泌肿瘤中也描述了另一种GTP结合蛋白Gi2α亚基的突变（gip突变）。在本研究中，我们检测了21例无功能垂体肿瘤和4例大催乳素瘤中的gsp突变，以及27例无功能肿瘤和4例大催乳素瘤中的gip突变。使用聚合酶链反应和变性梯度凝胶电泳，在分析Gsα基因时，2例无功能垂体肿瘤显示出迁移异常。对这些异常迁移的聚合酶链反应产物进行序列分析，发现了两个先前已知的gsp突变：密码子201处的精氨酸变为半胱氨酸，密码子227处的谷氨酰胺变为亮氨酸。未发现gip突变。这些发现强调了无功能垂体肿瘤的单克隆起源，并提示cAMP可能在无功能垂体肿瘤的肿瘤发生中起作用。
