Namba H, Matsuo K, Fagin J A
Department of Medicine, University of California, Los Angeles School of Medicine 90048.
J Clin Invest. 1990 Jul;86(1):120-5. doi: 10.1172/JCI114673.
We determined clonality of thyroid tumors from female patients who had restriction fragment length polymorphisms (RFLP) in the X chromosome genes hypoxanthine phosphoribosyltransferase (HPRT) or phosphoglycerate kinase (PGK). We screened normal thyroid tissue from 59 female patients; of the informative cases 14 were heterozygous for a Bgl I site on PGK and 4 were heterozygous for a Bam HI site on HPRT. In monoclonal tumors, one of the polymorphic alleles was selectively digested after additional digestion with Hpa II, a methylation sensitive enzyme, whereas in polyclonal tissue both were decreased to a similar extent. Normal thyroid tissue from all patients showed a polyclonal pattern. Of the 18 tumors studied, 12 were solitary thyroid nodules, and 6 were obtained from multinodular goiters (MNG). The following were monoclonal: 6/6 follicular adenomas, 2/2 follicular carcinomas, and 1/1 anaplastic carcinoma. Two of the three papillary carcinomas showed intermediate patterns, possibly due to contaminating effects of stromal tissue present in most of these neoplasms. Of the six nodules from MNG, four were polyclonal. The two largest gave a distinct monoclonal pattern. Most solitary thyroid tumors are monoclonal, supporting a somatic cell mutation model of thyroid neoplasm formation. Nodules from MNG are largely hyperplastic, although monoclonal neoplasms do occasionally arise within these glands. The specific somatic mutations leading to clonal expansion and determination of tumor phenotype are presently unknown.
我们对患有X染色体基因次黄嘌呤磷酸核糖转移酶（HPRT）或磷酸甘油酸激酶（PGK）限制性片段长度多态性（RFLP）的女性患者的甲状腺肿瘤进行了克隆性检测。我们筛选了59名女性患者的正常甲状腺组织；在信息丰富的病例中，14例PGK上的Bgl I位点杂合，4例HPRT上的Bam HI位点杂合。在单克隆肿瘤中，用甲基化敏感酶Hpa II进一步消化后，其中一个多态性等位基因被选择性消化，而在多克隆组织中，两者均以相似程度减少。所有患者的正常甲状腺组织均显示多克隆模式。在研究的18个肿瘤中，12个是孤立性甲状腺结节，6个取自多结节性甲状腺肿（MNG）。以下是单克隆的：6/6滤泡性腺瘤、2/2滤泡性癌和1/1间变性癌。三个乳头状癌中有两个显示中间模式，可能是由于这些肿瘤大多数中存在的基质组织的污染作用。在MNG的六个结节中，四个是多克隆的。两个最大的结节呈现出明显的单克隆模式。大多数孤立性甲状腺肿瘤是单克隆的，支持甲状腺肿瘤形成的体细胞突变模型。MNG的结节大多是增生性的，尽管这些腺体中偶尔也会出现单克隆肿瘤。目前尚不清楚导致克隆性扩增和肿瘤表型确定的具体体细胞突变。
