GENETIC ALTERATIONS DURING GASTRIC TUMOR DEVELOPMENT

在此之前阶段产生的流行病学和实验室数据 研究项目显示人类胃癌发生进展 通过一系列的六个阶段，形态特征和 生化标志物和分化的生化标志物定义了 进展为恶性。从正常状态到肿瘤状态的进展 发生在一段多年的时间里，在 调节力量包括致癌物、刺激物、细菌感染、 保护剂和遗传易感性。在拟议的研究中， 将尝试确定关键的遗传事件在 胃癌的发生，并确定它们是否类似于 以前在结直肠癌和其他癌症中发现的那些 纸巾。调查将集中在激活的特定标志物上 原癌基因的选择与抑癌基因的失活 参与肿瘤发生的过程。特定的遗传终结点 研究内容如下：ras基因体细胞突变在胃病发生中的作用 Ha-ras、Ki-ras和Ha-ras基因激活突变的致癌作用 不同发育阶段胃粘膜DNA中N-ras基因的表达 胃癌；胃粘膜DNA中p53基因的分析 等位基因缺失或点突变在肿瘤发生的不同阶段 基因的高度保守区，以确定是否 P53基因功能失活参与了胃癌的发生和发展 TPR-MET癌基因重排的发生频率和 C-met在胃癌发生发展不同阶段的表达水平。

Epidemiological and laboratory data produced in previous phases of this research program have shown human gastric carcinogenesis to progress through a series of six stages in which morphological features and biochemical markers and biochemical markers of differentiation define the progression to malignancy. The progression from normal to neoplastic state takes place over a period of many years, under the combined influence of modulating forces including carcinogens, irritants, bacterial infection, protective agents, and genetic susceptibility. In the proposed studies, attempts will be made to identify critical genetic events in the development of gastric cancer, and to determine whether they are similar to those previously found in colorectal cancer as well as cancers of other tissues. The investigation will focus on specific markers of activation of selected proto-oncogenes and inactivation of suppressor gene putatively involved in the tumorigenesis process. Specific genetic endpoints to be studied are: the role of somatic mutations in ras genes during gastric carcinogenesis by elucidation of activating mutations in Ha-ras, Ki-ras and N-ras genes in DNA of gastric mucosa at each stage of development of gastric cancer; analysis of the p53 gene in DNA of gastric mucosa at various stages of tumorigenesis for allelic deletions or point mutations in highly conserved regions of the gene in order to determine whether inactivation of p53 gene function is involved in gastric carcinogenesis and the frequency of occurrence of the TPR-MET oncogene rearrangement and expression levels of c-MET in the various stages of gastric carcinogenesis.