CLONING AND CHARACTERIZATION OF HUMAN CHROMOSOME 3P TUMOR SUPPRESSOR GENES

发育过程中染色体3p序列的持续缺失 包括肺癌和肾细胞癌在内的许多实体瘤的进展和进展 癌症促使研究人员检查 3 号染色体的短臂以发现 肿瘤抑制基因的存在。 然而，似乎有 至少三个不同的染色体区域：3p13-p14、3p21 和 3p25 在不同的实体瘤中被删除。 因此似乎至少有 3p 染色体上的三个不同的肿瘤抑制基因座。 第一个目标是 因此，实验室的任务是定位、克隆和表征 这些基因。 染色体带 3p14.2 包含一个常见的脆弱位点，该位点已被 被描述为人类基因组中最活跃的脆弱位点。 脆弱 位点可能使染色体容易断裂并随后导致 DNA 丢失 序列，因此 3p14.2 脆弱位点可能负责染色体 在许多实体瘤中观察到 3p 易位和/或缺失。 一个大 家庭被描述为宪法易位 t(3:8) (p14.2;q24.13) 肾细胞癌的发病率很高。 我们希望 从分子角度定义 3p14.2 脆弱区域周围的 DNA 序列 位点和家族性肾细胞癌易位断点（也 在 3p14.2 内）确定： (A) 特定位点染色体是否脆弱 断点在分子水平上聚集； (B) 如果是家族性肾细胞 癌断点位于包含脆弱位点特异性的区域内 断点； (c)染色体脆性的分子机制。 这些项目和熟练的分子生物学家组成的大型实验室 为学生学习现代化提供理想的实训环境 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.