TUMOR SUPPRESSOR GENES IN HUMAN HEPATOCELLULAR CARCINOMA

人类肝细胞癌中的抑癌基因

• 批准号: 3752737
• 负责人: E TABOR
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752737
• 关键词: Europe; adenoma; gene expression; gene mutation; genetic polymorphism; hepatoblastoma; hepatocellular carcinoma; human genetic material tag; human tissue; hyperplasia; immunocytochemistry; molecular cloning; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction; southeast Asia; tumor suppressor genes

Studies of p53 mutations in hepatocellular carcinoma (HCC) have continued. Results from previous studies in this laboratory in patients from China and the U.S. were continued in patients from Europe. p53 expression was studied by immunohistochemical methods in benign and malignant human epithelial liver lesions in 46 patients from Hungary (16 hepatocellular carcinomas, 7 hepatoblastomas, 17 focal nodular hyperplasias, and 6 hepatocellular adenomas). Positive immunostaining for p53 protein, indicating the probable presence of a mutation in the p53 gene, was detected in the nuclei of tumor cells of seven of 16 HCC patients (44%). Immunostaining of p53 was seen in one of seven hepatoblastomas, none of 17 focal nodular hyperplasias, and none of six hepatocellular adenomas, indicating that these other liver lesions probably do not frequently have p53 mutations. In the liver tissue adjacent to all the tumors studied, hepatocytes did not stain for the presumed mutant p53 protein. The detection of mutant p53 in a relatively high percentage of the HCC cases in Hungary, a country in which aflatoxin contamination of the diet is rare, suggests that factors other than aflatoxin led to p53 mutations in these patients. p53 gene mutations appear to be uncommon in hepatoblastoma and benign liver lesions such as focal nodular hyperplasia and hepatocellular adenoma. Studies using single-strand conformation polymorphism (SSCP) and sequencing are being used to identify p53 mutations in HCC patients from Hungary, Korea, and the USA (Texas; NIH; Hawaii). In Korean patients, 14/35 patients (46%) have p53 mutations. In patients from Texas, mutations have been found so far in 3/22 patients (14%), although additional studies are in progress. In addition, wild-type p53 has been cloned to produce reagent materials for other studies, including studying the binding of p53 to cellular proteins and nucleotides.

肝细胞癌（HCC）中p53突变的研究已经 持续期间内的 本实验室先前在患者中进行的研究结果 在欧洲患者中继续使用来自中国和美国的药物。 p53 用免疫组化方法研究了乳腺良性病变和 来自匈牙利的46名患者（16 肝细胞癌，7例肝母细胞瘤，17例局灶性结节性 增生和6例肝细胞腺瘤）。 阳性表达 对于p53蛋白，这表明可能存在突变， p53基因在7/16例HCC的肿瘤细胞核中表达 患者（44%）。 p53免疫染色见于7例中的1例。 肝母细胞瘤，17例局灶性结节增生和6例 肝细胞腺瘤，表明这些其他肝脏病变 可能不经常发生p53突变。 肝组织中 在所有研究的肿瘤附近，肝细胞没有染色。 推测的突变型p53蛋白。 突变型p53基因的检测是一个相对复杂的过程。 匈牙利的HCC病例比例很高， 饮食中的污染是罕见的，这表明， 黄曲霉毒素导致这些患者的p53突变。 p53基因突变 在肝母细胞瘤和良性肝脏病变中似乎不常见， 局灶性结节增生和肝细胞腺瘤。 利用单链构象多态性（SSCP）和 测序被用于鉴定HCC患者中的p53突变， 匈牙利、韩国和美国（德克萨斯州; NIH;夏威夷）。 在韩国患者中， 14/35例患者（46%）有p53突变。 在德克萨斯州的病人中， 到目前为止，在3/22例患者（14%）中发现了突变，尽管 其他研究正在进行中。 此外，野生型p53已被克隆以产生试剂材料 对于其他研究，包括研究p53与细胞的结合， 蛋白质和核苷酸。