CLONAL COMPOSITION OF BENIGN AND MALIGNANT HUMAN THYROID-TUMORS
CLONAL COMPOSITION OF BENIGN AND MALIGNANT HUMAN THYROID-TUMORS
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DOI：
10.1172/jci114673
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发表时间：
1990-07-01
影响因子：
15.9
通讯作者：
FAGIN, JA
中科院分区：
文献类型：
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作者：
NAMBA, H;MATSUO, K;FAGIN, JA
我们测定了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）存在限制性片段长度多态性（RFLP）的女性甲状腺肿瘤患者的克隆性。我们从59例女性患者中筛选出正常甲状腺组织，其中14例为PGK上Bgl I位点杂合子，4例为HPRT上Bam HI位点杂合子。在单克隆肿瘤中，一个多态性等位基因被选择性消化后，额外的消化与Hpa II，甲基化敏感酶，而在多克隆组织都减少到类似的程度。所有患者的正常甲状腺组织显示多克隆模式。在18例甲状腺肿瘤中，12例为孤立性甲状腺结节，6例为多结节性甲状腺肿（MNG）。以下为单克隆：6/6滤泡性腺瘤，2/2滤泡性癌和1.1未分化癌。三个乳头状癌中的两个显示中间模式，可能是由于大多数肿瘤中存在的间质组织的污染作用。在MNG的6个结节中，4个是多克隆的。两个最大的给出了不同的单克隆模式。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的结节大部分是增生性的，尽管在这些腺体内偶尔发生单克隆肿瘤。导致克隆扩增和确定肿瘤表型的特定体细胞突变目前尚不清楚。
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 mutlinodular 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 thee neoplasms. Of the six nodules from MNG, four were polyclonal. The two largest gave a distinct monoclonal pattern. Most solitary thyroid tumors are monclonal, 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.