Arnold A, Kim H G
Endocrine Unit, Massachusetts General Hospital, Boston 02114.
J Clin Endocrinol Metab. 1989 Sep;69(3):496-9. doi: 10.1210/jcem-69-3-496.
Traditional cytogenetic approaches have been unsuccessful in the study of parathyroid adenomas. We now describe one parathyroid adenoma in which a molecular cytogenetic approach revealed clonal loss of one chromosome 11. Restriction fragment length polymorphism analysis of the patient's normal leukocyte DNA demonstrated heterozygosity at four loci (PTH, INT2, APOA1, and ETS1) that span the length of chromosome 11. However, the adenoma DNA showed clonal deletion of one allele, i.e. loss of heterozygosity, at each locus. Use of five nonpolymorphic probes from chromosome 11 was consistent with 50% loss of total chromosome 11 DNA in the adenoma. No tumor-specific loss of heterozygosity was observed when restriction fragment length polymorphisms from five other autosomes (no. 1, 5, 6, 7, and 12) were analyzed, and an X-chromosome probe also showed no tumor DNA loss. We have demonstrated tumor-specific chromosome loss in a parathyroid adenoma; such a lesion has been described only rarely in benign tumors. Our finding adds to the evidence for monoclonality in parathyroid adenomatosis, indicates that only one PTH gene copy is sufficient for hyperparathyroid tumor function, and raises the possibility that a tumor-suppressor gene important in the development of nonfamilial parathyroid neoplasia is located on chromosome 11.
传统的细胞遗传学方法在甲状旁腺腺瘤的研究中并不成功。我们现在描述一例甲状旁腺腺瘤，采用分子细胞遗传学方法发现11号染色体出现克隆性缺失。对患者正常白细胞DNA进行的限制性片段长度多态性分析显示，在跨越11号染色体全长的四个位点（甲状旁腺激素、INT2、载脂蛋白A1和ETS1）呈杂合性。然而，腺瘤DNA在每个位点均显示一个等位基因的克隆性缺失，即杂合性缺失。使用来自11号染色体的五个非多态性探针，结果与腺瘤中11号染色体总DNA丢失50%一致。分析来自其他五条常染色体（1、5、6、7和12号）的限制性片段长度多态性时，未观察到肿瘤特异性杂合性缺失，并且一个X染色体探针也未显示肿瘤DNA丢失。我们已经证实在一例甲状旁腺腺瘤中存在肿瘤特异性染色体缺失；这种病变在良性肿瘤中仅被罕见报道。我们的发现为甲状旁腺腺瘤病的单克隆性提供了更多证据，表明仅一个甲状旁腺激素基因拷贝就足以维持甲状旁腺肿瘤的功能，并增加了一种在非家族性甲状旁腺肿瘤发生中起重要作用的肿瘤抑制基因位于11号染色体上的可能性。
