Kobayashi H, Usui T, Fukata J, Yoshimasa T, Oki Y, Nakao K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Endocr J. 2000 Aug;47(4):461-6. doi: 10.1507/endocrj.47.461.
While the mechanisms of tumorigenesis for adrenocortical neoplasms remain unknown, several genes, such as Gsalpha, ACTH receptor (MC2-R), p53, and p16 tumor suppressor genes, are considered to be candidates for adrenocortical neoplasms. Mutation analysis studies have documented these genes in adrenocortical neoplasms, but these studies focused on the mutation of only one of these genes. In the present study we examined the mutations of three of these genes (Gsalpha, MC2-R, and p53) in adrenocortical neoplasms in Japanese patients. We amplified these genes using polymerase chain reaction and directly sequenced them in 30 functioning adrenocortical neoplasms. As for Gsalpha, we identified a heterogeneous substitution of glutamine to histidine at codon 227 and a gain of an Nru I restriction endonuclease site. The mutation was restricted to adenomatous tissue, and did not occur in the adjacent normal adrenal tissue or leukocytes of the patient. We did not find any mutations in MC2-R and p53. In conclusion, although the contribution of these three genes to adrenocortical tumorigenesis remains to be determined, it is suggested that the mutation of Gsalpha might play a role in functional adrenocortical neoplasms.
虽然肾上腺皮质肿瘤的肿瘤发生机制尚不清楚，但一些基因，如Gsα、促肾上腺皮质激素受体（MC2-R）、p53和p16肿瘤抑制基因，被认为是肾上腺皮质肿瘤的候选基因。突变分析研究已在肾上腺皮质肿瘤中记录了这些基因，但这些研究仅聚焦于其中一个基因的突变。在本研究中，我们检测了日本患者肾上腺皮质肿瘤中这三个基因（Gsα、MC2-R和p53）的突变情况。我们使用聚合酶链反应扩增这些基因，并对30例功能性肾上腺皮质肿瘤进行直接测序。至于Gsα，我们在密码子227处鉴定到谷氨酰胺到组氨酸的异质性替代以及Nru I限制性内切酶位点的获得。该突变局限于腺瘤组织，未出现在患者的相邻正常肾上腺组织或白细胞中。我们在MC2-R和p53中未发现任何突变。总之，尽管这三个基因对肾上腺皮质肿瘤发生的作用尚待确定，但提示Gsα的突变可能在功能性肾上腺皮质肿瘤中起作用。
