Molecular Pathology of Solid Tumors in Childhood

儿童实体瘤的分子病理学

基本信息

批准号：
10307004
负责人：
HATA Jun-ichi
金额：
$ 24.64万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

We performed molecular pathological analysis of embryonal tumors such as germ cell tumors, Wilms tumors and Ewing/PNET tumors which are thought to be derived from embryonal tissue during.1, we originally isolated EAT (early gene induced by all trans retinoic acid) gene from embryonal carcinoma cell lines (NCR-G3). Sequencing analysis revealed that EAT possessed BH1 and BH2 domains suggesting a bcl family gene. This gene was shown to have antiapoptotic functions by vitro and in vivo studies. Northern analysis and immunohistochemical studies disclosed that he EAT gene distributed in a variety of fetal and adult tissues including stage of early embryogenesis. EAT gene was shown to exclusively localize in the external and internal membrane of mitochondria by using immunoelectron microscopic procedures. These findings suggested that this gene play an important role in maintenance of early embryogenesis through antiapoptotic functions.2, Wilms tumor are a typical embryonal tumors that is der … More ived from metanephric blastoma and the most common renal tumors in childhood. Novel gene, WT1, has been isolated chromosome11p13 region as a responsible gene in oncogenesis of Wilms tumor. This gene also play an important role in normal nephrogenesis and gonadal developments, especially male genital organs. Denys-Drash syndrome characterized by association of Wilms tumor, early onset and progressive renal failure and urogenital anomalies. Recent studies showed that exonic mutations at zinc finger domains of WT1 is responsible for pathogenesis of this syndrome. We analyzed WT1 mutations in 18 clinically diagnosed "Denys-Drash"(Drash) syndrome cases. 9 cases were typical Drash syndrome. Whereas another cases showed inronic point mutations at the splicing donor site at exon9. These mutations affect alternative splicing. The isoforms retaining three amino acids, KTS, are not produced. Clinical features of the patients with the intronic mutations correlated well with those of Frasier syndrome, characterized by more slowly progressing nephropathy than Denys-Drash syndrome, associated streak gonads and no development of Wilms' tumor. Our results indicate that WT1 isoforms with or without KTS have different functions in tumorigenesis and organogenesis of kidneys and gonads. Less

我们对胚胎，Wilms肿瘤和EWING/PNET肿瘤进行了分子病理分析，而在1期间，我们是从胚胎组织中进行的。我们最初是从胚胎癌细胞系（NCR-癌细胞系（NCR-癌细胞）基因诱导的（所有跨性别视黄度酸）基因（NCR-癌细胞）的早期基因（NCR-- G3如何通过体内分析和免疫组织化学研究来揭示出在早期胚胎发生的多种胎儿组织中，可以揭示出分布的基因通过抗抑制作用的早期胚胎发生在儿童时期中最常见的肾脏肿瘤。 Wilms肿瘤的表征，尿液肿瘤的早期肾脏衰竭和WT1的锌指域是综合征的发病率具有内含子突变的Ients酸是酸综合症SH综合征的Ients，我们的结果具有或没有KTS的带有潜水的Nctions的肿瘤和肾脏和肿瘤的有机化。