Alexander J M, Biller B M, Bikkal H, Zervas N T, Arnold A, Klibanski A
Division of Medicine, Massachusetts General Hospital, Boston 02114.
J Clin Invest. 1990 Jul;86(1):336-40. doi: 10.1172/JCI114705.
Clinically nonfunctioning pituitary adenomas are benign neoplasms comprising approximately 25-30% of pituitary tumors. Little is known about the pathogenesis of pituitary neoplasia. Clonal analysis allows one to make the important distinction between a polyclonal proliferation in response to a stimulatory factor versus a monoclonal expansion of a genetically aberrant cell. We investigated the clonal origin of pituitary tumors using X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase and hypoxanthine phosphoribosyl-transferase genes. Restriction enzymes were used to distinguish maternal and paternal X-chromosomes, and combined with a methylation-sensitive restriction enzyme to analyze allelic X-inactivation patterns in six pituitary adenomas. All six tumors showed a monoclonal pattern of X-inactivation. These data indicate that nonfunctioning pituitary adenomas are unicellular in origin, a result consistent with the hypothesis that this tumor type is due to somatic mutation.
临床上无功能垂体腺瘤是良性肿瘤，约占垂体肿瘤的25% - 30%。垂体肿瘤的发病机制知之甚少。克隆分析能够在因刺激因子引起的多克隆增殖与基因异常细胞的单克隆扩增之间做出重要区分。我们利用磷酸甘油酸激酶和次黄嘌呤磷酸核糖转移酶基因处的X连锁限制性片段长度多态性来研究垂体肿瘤的克隆起源。使用限制性内切酶区分母本和父本X染色体，并结合甲基化敏感的限制性内切酶分析6例垂体腺瘤中的等位基因X失活模式。所有6个肿瘤均显示出X失活的单克隆模式。这些数据表明，无功能垂体腺瘤起源于单细胞，这一结果与该肿瘤类型是由体细胞突变引起的假说一致。
