GENETIC CHANGES IN PRIMARY HEPATOCELLULAR CARCINOMA

原发性肝细胞癌是一种常见的恶性肿瘤 其肿瘤发生模式目前尚不清楚。 初步 然而，研究表明，肿瘤的遗传变化 与隐性事件一致。 这些发现表明 隐性致癌机制在PHC中可能是重要的。 这项研究的总体目标是确定遗传变化 发生于原发性肝肿瘤。 一种分子遗传核型 将从大约100个PHC肿瘤的集合中得出 通过对多态性标记位点和候选基因的RFLP进行分型， 分布在整个人类基因组中。 这种分子遗传学 核型将允许评估的遗传组成， PHC肿瘤基因组目前不可能通过标准 细胞遗传学技术 具体而言，观察到的变化将是 用于对隐性模型进行综合检验， 原发性肝癌的肿瘤发生 候选基因座的系统调查将 允许评估孤立报告的重要性， 癌基因或生长因子的改变。 分子遗传学核型的信息也将 与临床变量相关，以评估其关节 在PHC中的意义 患者数据显示， 病史和临床表现。 目前还不清楚 这种变异在多大程度上反映了 肿瘤 观察到一致的细胞遗传学差异， 造血肿瘤已被证明可用于分类， 在治疗中很重要。 这项研究将试图 确定遗传因素是否也具有临床重要性， PHC。

Primary hepatocellular carcinoma (PHC) is a common malignancy whose mode of oncogenesis is currently unknown. Preliminary studies have shown, however, genetic changes in tumors consistent with recessive events. These findings suggest that recessive oncogenic mechanisms may be important in PHC. The overall goal of this research is to ascertain genetic changes occurring in primary liver tumors. A molecular genetic karyotype will be derived for a collection of approximately 100 PHC tumors by typing RFLPs for polymorphic marker loci and candidate genes distributed throughout the human genome. This molecular genetic karyotype will permit evaluation of the genetic constitution of PHC tumor genomes not currently possible by standard cytogenetic techniques. Specifically, observed changes will be used to make a comprehensive test of the recessive model of oncogenesis in PHC. A systematic survey of candidate loci will permit evaluation of the significance of isolated reports of oncogene or growth factor changes in PHC. The information from the molecular genetic karyotypes will also be correlated with clinical variables to evaluate their joint significance in PHC. Patient data show wide variation in natural history and clinical presentation of disease. It is not known to what extent this variation reflects underlying genetic variation of the tumors. Observation of consistent cytogenetic differences in hematopoietic tumors has proven useful in classification and promises to be important in treatment. This study will attempt to determine if genetic factors are also of clinical importance in PHC.