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Genetic Events Associated With Choriocarcinogenesis.

与绒毛膜癌发生相关的遗传事件。

基本信息

批准号：
07042006
负责人：
WAKE Norio
金额：
$ 4.99万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07042006/
关键词：
Complete mole Choriocarcinoma Genetic origin genome imprinting IGF2-H19 microcell fusion tumor suppressor gene (s)Chromosome7 両側アリルの欠失共通欠失領域 IGF2 H19 インプリンティング胞状奇胎絨毛

项目摘要

We investigated 1. genetic origin of choriocarcinoma, 2. association of IGF2 and H19 imprinting with choriocarcinoma and 3. location of tumor suppressor gene (s) on human chromosome 7.1. The genetic origin of 24 trophoblastic neoplasms was determined by using PCR polymorphisms. Based on pregnancy history, the tumor included 9 postmolar trophoblastic tumors. Androgenetic origin was defined in 8 tumors, and the remaining one might have arisen from a normal fertilization. Six tumors retained genetic features carried by the homozygous complete mole. Two showed PCR polymorphisms compatible with that of the heterozygous complete mole. Our results support the suggestion that of all forms of pregnancy that predispose patients to choriocarcinoma, the most likely is the complete mole. Uniparental or monoallelic transmission of the genome that would render a particular type of tumor suppressor gene susceptible to functional inactivation may correspond to the propensity to malignancy in complete m … More ores. 2. We studied IGF2 and H19 expression, and methylation status of H19 in choriocarcinomas. Choriocarcinomas were characterized by a low expression of IGF2 and a high expression of H19. Biallelic expression of IGF2 or H19 was found frequently. Contrary to expectation, enhanced H19 expression was accompanied by hypermethylation of CpG sites over the entire gene region, apparently being at variance with the finding in normal placentae and androgenetic moles. The findings provide the possibility that the mutated promoter is responsible for overcoming transcriptional suppression by CpG methylation in the H19 gene. 3. To determine the chromosome carrying putative tumor suppressor gene (s), a single human chromosome was transferred into choriocarcinoma cells. Microcell-hybrids containing chromosome 7 were suppressed or modulated for tumorigenicity and exhibited altered in vitro growth properties, suggesting that chromosome 7 contains a putative tumor suppressor gene (s) for choriocarcinoma. In addition, we obtained evidence to define a critical region on chromosome 7 that was frequently lost in surgically removed choriocarcinoma tissues and cell lines. Using a panel of microsatellite markers, biallelic deletions were observed, which strongly suggests the presence of a tumor suppressor gene (s) within this critical region. Less

我们调查了1。绒毛膜癌的遗传起源，2. IGF 2和H19印迹与绒毛膜癌的关系;肿瘤抑制基因在人类7.1号染色体上的位置。应用聚合酶链反应（PCR）多态性技术对24例滋养细胞肿瘤的遗传起源进行了研究。根据妊娠史，肿瘤包括9个磨牙后滋养细胞肿瘤。雄激素源性肿瘤中定义8个，和剩余的一个可能已经出现了一个正常的受精。六个肿瘤保留了纯合子完全痣的遗传特征。2例显示与杂合子完全性葡萄胎相一致的PCR多态性。我们的研究结果支持这样的建议，即所有形式的怀孕，使患者容易患绒毛膜癌，最有可能是完整的痣。基因组的单亲或单等位基因传递使特定类型的肿瘤抑制基因易于功能失活，这可能与完全性乳腺癌的恶性倾向相对应。 ...更多信息石. 2.我们研究了绒毛膜癌中IGF 2和H19的表达，以及H19的甲基化状态。绒毛膜癌的特点是IGF 2的低表达和H19的高表达。IGF 2或H19的双等位基因表达频繁。与预期相反，增强H19表达伴随着整个基因区域的CpG位点的超甲基化，显然与正常胎盘和雄激素痣的发现不同。这一发现提供了一种可能性，即突变的启动子负责克服H19基因中CpG甲基化引起的转录抑制。3.为了确定携带假定的肿瘤抑制基因的染色体，将单个人染色体转移到绒毛膜癌细胞中。含有7号染色体的微细胞杂交体的致瘤性被抑制或调节，并表现出体外生长特性的改变，这表明7号染色体含有绒毛膜癌的推定肿瘤抑制基因。此外，我们获得的证据，以确定一个关键区域的7号染色体上，这是经常失去手术切除绒毛膜癌组织和细胞系。使用一组微卫星标记，观察到双等位基因缺失，这强烈表明在这个关键区域内存在肿瘤抑制基因。少