Analysis of menin gene in human neoplasms.

甲状旁腺肿瘤与增生很难鉴别。为了阐明尿毒症甲状旁腺增生的克隆性和分子遗传异常占克隆出现，我们分析了20例尿毒症甲状旁腺增生。用X染色体连锁的人雄激素受体（HUMARA）基因和磷酸甘油酸激酶（PGK）基因确定克隆性，通过研究11 q13的杂合性缺失（洛）和MEN 1基因的体细胞突变来分析多发性内分泌瘤1型（MEN 1）基因异常。作为阳性对照，同时分析一例患有Zollinger-Ellison综合征的MEN 1病例。我们的分析表明，大多数（75%）尿毒症性甲状旁腺增生组织，包括复发性甲状旁腺增生的自体移植物，是单克隆起源的。克隆性与血清羧基末端甲状旁腺激素（C-PTH）水平、钙水平、血液透析持续时间、腺体重量或病理特征无关。未发现11 q13的洛缺失和MEN 1基因的体细胞突变。对于MEN 1病例，在外显子3中检测到生殖系突变（W198 X）。我们的结论是，大多数尿毒症甲状旁腺增生的情况下，实际上是单克隆瘤。MEN 1基因异常在尿毒症甲状旁腺增生的克隆出现中起次要作用。

It is difficult to differentiate between parathyroid neoplasia and hyperplasia. In an attempt to elucidate the clonality of uremic parathyroid hyperplasia and the molecular genetic abnormalities accounting for clonal emergence, we analyzed 20 cases of uremic parathyroid hyperplasia. Clonalities were determined using the X-chromosome-linked human androgen receptor(HUMARA) gene and the phosphoglycerate kinase(PGK) gene, and multiple endocrine neoplasia type1(MEN1) gene abnormality was analyzed by studying loss of heterozygosity(LOH) in 11q13 and somatic mutations in the MEN1 gene. As a positive control, a case of MEN1 with Zollinger-Ellison syndromes was analyzed simultaneously. Our analysis revealed that a majority(75%)of theuremic parathyroid hyperplasia tissues, in-cluding an autograft with recurrent hyperparathyroidism, was of monoclonal orig-in. Clonality did not correlate with serum carboxyl-terminal parathyroid hormone(C-PTH) level, calcium level, hemodialytic duration, gland weight or pathological features. Neither LOH in 11q13 nor somatic mutation in the MEN1 gene was detected. For the MEN1 case, a germline mutation(W198X)was detected In exon3. We concluded that a majority of the uremic parathyroid hyperplasia cases was in fact monoclonal naeoplasia. MEN1 gene abnormality played a minor role, if any, in the clonal emergence in uremic parathyroid hyperplasia.