GENETIC ALTERATIONS DURING GASTRIC TUMOR DEVELOPMENT

胃肿瘤发展过程中的基因改变

• 批准号: 3729699
• 负责人: GERALD N WOGAN
• 金额: --
• 依托单位: LSU HEALTH SCIENCES CENTER
• 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/3729699
• 关键词: biopsy; carcinogenesis; carcinoma; computer simulation; gastric mucosa; gastritis; gel electrophoresis; gene induction /repression; gene mutation; gene rearrangement; human subject; metaplasia; molecular cloning; molecular oncology; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplastic transformation; nucleic acid sequence; oncogenes; polymerase chain reaction; preneoplastic state; protooncogene; restriction fragment length polymorphism; stomach neoplasms; tumor suppressor genes; western blottings

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.

在此之前阶段产生的流行病学和实验室数据 研究计划表明人类胃癌发生进展 通过一系列的六个阶段，其中形态特征和 生化标记和分化生化标记定义了 进展为恶性肿瘤。 从正常状态到肿瘤状态的进展 发生在多年的综合影响下 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 胃癌的发展，并确定它们是否与胃癌相似 以前在结直肠癌以及其他癌症中发现的那些 组织。 调查将集中于激活的特定标志物 选择原癌基因并假定抑制基因失活 参与肿瘤发生过程。 具体的遗传终点 研究的内容是： ras 基因体细胞突变在胃病过程中的作用 通过阐明 Ha-ras、Ki-ras 和 Ki-ras 的激活突变来致癌 各发育阶段胃粘膜DNA中的N-ras基因 胃癌；胃粘膜 DNA 中 p53 基因的分析 等位基因缺失或点突变的肿瘤发生的各个阶段 基因的高度保守区域，以确定是否 p53基因功能失活与胃癌发生有关 TPR-MET癌基因重排的发生频率和 c-MET在胃癌发生各阶段的表达水平