Clonarity analysis on hyperparathyroidism

甲状旁腺功能亢进症克隆性分析

基本信息

批准号：
09670199
负责人：
KAKUDO Kennichi
金额：
$ 1.92万
依托单位：
Wakayama Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670199/
关键词：
hyperparathyroidism parathyroid Pathology Clonarity p53 gene MEN 1 gene ret oncoger mutation p53 gene MEN1 gene ret oncogene 原発性副甲状腺機能亢進症二次性副甲状腺機能亢進症 clonality menin gene

项目摘要

Purpose : To differentiate between morioclonal neoplasia and polyclonal hyperplasia arising in the primary and secondary hyperparathyroidism (PHPT and SHPT) and to elucidate the molecular basis responsible for the neoplastic proliferation.Materials and Methods : The surgical materials of parathyroids obtained from the patients with PHPT and SHPT were investigated using molecular genetic analysis.Results : 1. The neoplastic lesion usually showed a homogeneous distribution of the PTH hormone versus heterogeneous in hyperplastic lesion in immunohistochemistry. 2. By X-linked PGK and HUMARA gene inactivation analysis, almost all of the parathyroid adenomas were demonstrated to be of monoclonal origin. Contrary to the traditional histological crieria, majority of the primary (2/2) and secondary multigland hyperplasia (19/27, 70.4%) were also of monoclonal origin. A progression from polyclonal hyperplasia to monoclonal neoplasia might be present in the development of SHPT.3. Different parath … More yroid disorders were related to different genetic abnormalities. 1). Not only in parathyroid carcinomas, but also in parathyroid adenomas, particularly those with nuclear pleomorphism, were detected overexpression of p53 protein (4/32), somatic mutation (R290H), polymorphism (L252L,R72P) and LOH.2). Abnormality of MEN 1 gene (W1 98X, A340T, A541T, T429K, D418D, V367V) was identified in both MEN 1 and sporadic endocrin tumors (parathyroid adenoma and pancreatic endocrine tumor), but only in less than 20% of parathyroid adenomas. 3). Different from MEN 1 gene, ret oncogene mutation seemed to be unrelated to parathyroid adenomas (0/16), although its somatic mutation was found in 32.5% (13/40) of thyroid medullary carcinoma. 4). In the parathyroids (20 glands) with SHPT, we have failed to find any abnormalities of p53, MEN 1 and 1 p35-36.Conclusion : 1. Parathyroid adenomas are of monoclonal origin, related to multiple genetic abnormalities. 2. Clonal analysis suggests a progression from polyclonal hyperplasia to monoclonal neoplasia in the SHPT with unknown genetic abnormality. 3. The distribution pattern of PTH hormone protein, clonality and genetic analysis are helpful in the differentiation between hyperplastic lesions and neoplasia. Less

目的：在主要和继发性甲状旁腺功能亢进症（PHPT和SHPT）中区分垂直性肿瘤和多克隆增生，并阐明负责对pHyroult和SHPPT的副层的分析材料的分子材料的分子基础。肿瘤病变通常显示出在免疫组织化学中PTH激素与异质性病变中的异质性的均匀分布。 2。通过X连锁的PGK和Humara基因失活分析，几乎所有甲状旁腺腺瘤几乎被证明是单克隆的起源。与传统的组织学CRIERIA相反，大多数主要（2/2）和二级多岩增生（19/27，70.4％）也是单克隆的起源。 SHPT的发展中可能存在从多克隆增生到单克隆肿瘤的发展。3。不同的parath…更多的YROID疾病与不同的遗传异常有关。 1）。不仅在甲状旁腺癌中，而且在甲状旁腺腺瘤，尤其是患有核多态性的甲状腺腺瘤中，都被检测到p53蛋白（4/32）的过表达（4/32），体细胞突变（R290H），多态性（L252L，R72P）和LOH.2）。男性1基因的异常（W1 98X，A340T，A541T，T429K，D418D，V367V）在男性1和孢子虫内分泌肿瘤（甲状旁腺腺瘤腺瘤和胰腺内分泌肿瘤）中都被鉴定出来，但仅在较小的parathymas of Parathyomas中。 3）。与男性1基因不同，RET癌基因突变似乎与甲状旁腺腺瘤（0/16）无关，尽管在32.5％（13/40）的甲状腺髓瘤中发现了体细胞突变。 4）。在带有shpt的甲状旁腺（20个腺体）中，我们未能发现p53，男子1和1 p35-36的任何异常。结论：1。甲状旁腺腺瘤是单氯烷的起源，与多种遗传异常有关。 2。克隆分析表明，在遗传异常未知的SHPT中，从多克隆增生到单克隆肿瘤的进展。 3。PTH同源蛋白，克隆性和遗传分析的分布模式有助于增生病变和肿瘤的分化。