CLONING AND CHARACTERIZATION OF HUMAN CHROMOSOME 3P TUMOR SUPPRESSOR GENES

染色体3p序列在发育过程中的持续缺失 以及包括肺癌和肾细胞在内的许多实体肿瘤的进展 癌症使研究人员对3号染色体的短臂进行了检查 肿瘤抑制基因的存在。然而，似乎有一种 至少三个不同的染色体区域，3p13-p14，3p21和3p25， 在不同的实体肿瘤中缺失。因此，似乎至少有 染色体3p上有3个不同的抑癌基因。的第一个目标 因此，实验室正在进行本地化、克隆和表征 这些基因。 染色体带3p14.2包含一个常见的脆性部位 被描述为人类基因组中最活跃的脆弱部位。易碎品 位点可能使染色体容易断裂并随后丢失DNA 序列，因此3p14.2脆性部位可能负责染色体 3P易位和/或缺失见于许多实体瘤。大号 家族性易位描述为t(3：8) (p14.2；q24.13)为肾癌高发区。我们希望 从分子上确定3p14.2脆性元件周围的DNA序列 部位和家族性肾细胞癌易位断裂点(也 在3p14.2内)以确定：(A)易碎部位特有的染色体 断点在分子水平上聚集；(B)如果家族肾细胞 癌断点位于包含脆性部位的区域内 (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 为学生学习现代提供理想的训练环境 分子方法论和科学实验原理。

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.