CLONING AND CHARACTERIZATION OF HUMAN CHROMOSOME 3P TUMOR SUPPRESSOR GENES

人类染色体 3P 肿瘤抑制基因的克隆和表征

• 批准号: 6107248
• 负责人: David I Smith
• 金额: $ 5.62万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107248
• 关键词: aphidicolin; chromosome deletion; chromosome translocation; chromosomes; cytogenetics; human genetic material tag; molecular cloning; nucleic acid sequence; radiotracer; renal cell carcinoma; tumor suppressor genes

The consistent deletion of chromosome 3p sequences during the development and progression of many solid tumors including lung cancer and renal cell carcinoma has led researchers to examine the short arm of chromosome 3 for the presence of tumor suppressor genes. However, there appear to be at least three distinct chromosomal regions, 3p13-p14, 3p21, and 3p25, that are deleted in different solid tumors. Thus there seems to be at least three distinct tumor suppressor loci on chromosome 3p. The first goals of the laboratory are therefore the localization, cloning and characterization of these genes. Chromosomal band 3p14.2 contains a common fragile site which has been described as the most active fragile site in the human genome. Fragile sites may predispose chromosomes to breakage and subsequent loss of DNA sequences, thus the 3p14.2 fragile site may be responsible for chromosome 3p translocations and/or deletions observed in many solid tumors. A large family was described with a constitutional translocation t(3:8) (p14.2;q24.13) that had a high incidence of renal cell carcinoma. We wish to molecularly define DNA sequences surrounding both the 3p14.2 fragile site and the familial renal cell carcinoma translocation breakpoint (also within 3p14.2) to determine: (A) if fragile site-specific chromosome breakpoints cluster at the molecular level; (B) if the familial renal cell carcinoma breakpoint is within the region containing fragile site-specific breakpoints; and (c) the molecular mechanism of chromosome fragility. These projects and a large laboratory of skilled molecular biologists provide the ideal training environment for students to learn modern molecular methodologies and the principles of scientific experimentation.

发育过程中染色体3 p序列的一致性缺失 以及许多实体瘤的进展，包括肺癌和肾细胞癌。 癌症促使研究人员检查3号染色体的短臂， 肿瘤抑制基因的存在。 然而，似乎在 至少三个不同的染色体区域，3 p13-p14，3 p21和3 p25， 在不同的实体瘤中缺失。 因此，似乎至少有 染色体3 p上的三个不同的肿瘤抑制基因座。 的第一个目标 因此，实验室的定位，克隆和表征 这些基因。 染色体带3p14.2含有一个共同的脆性位点， 被描述为人类基因组中最活跃的脆弱位点。 脆弱 位点可能使染色体易于断裂和随后的DNA丢失 因此，3p14.2脆性位点可能负责染色体 在许多实体瘤中观察到3 p易位和/或缺失。 大 该家族被描述为体质性易位t（3：8） （p14.2;q24.13）肾细胞癌发病率高。 我们希望 从分子上定义3p14.2脆性蛋白周围的DNA序列 位点和家族性肾细胞癌易位断点（也 在3p14.2内）以确定：（A）是否脆性位点特异性染色体 断裂点在分子水平聚集;（B）如果家族性肾细胞 癌断裂点在含有脆性位点特异性的区域内 断裂点;和（c）染色体脆性的分子机制。 这些项目和一个由熟练的分子生物学家组成的大型实验室 提供理想的培训环境，让学生学习现代 分子方法学和科学实验原理。