CHROMOSOME BREAKPOINTS & RENAL & SMALL CELL LUNG CANCER

人类3号染色体的特定重排已经被 与恶性和发育性有关 精神错乱。染色体3p14-21区域的缺失是一种 自发性肺癌的恒定细胞遗传学特征 肾脏和这个相同的区域参与了遗传性肾脏 3；8易位所致的癌。该地区也是一个 较大的缺失(3p14-23)与较小的 肺癌的细胞癌。染色体3p14.2也是 最常见的构成脆性部位的位置，可能 参与其中一些重排的致病过程。 我们建议为两个区域构造精确的限制图 在更大的删除区域内。第一个区域是从3p14.1- P14.2，第二个是3p21-p21.1。使用染色体3p- 我们将分离出足够多的宇宙体库 使这些区域完全饱和，每隔至少1个粘粒 1000千个碱基。衍生独特的序列杂交探针 将使用一组体细胞进行定位 定义和跨越这一地区的混血儿。已本地化的探测器 3p14.1-3p14.2和3p21-p21.1之间的关系也将分析为 找到离几个特定断点最近的宇宙。这些遗嘱 然后形成最终克隆的起点，并 这些断点的特征。这项工作应该有助于 分离与致病相关的关键区域 这些疾病以及设置启动的建设 基因组这一动态区域的完整限制图。

Specific rearrangements of human chromosome 3 have been characteristically associated with malignant and developmental disorders. Deletion of the chromosome 3p14-21 region is a constant cytogenetic feature in spontaneous carcinoma of the kidney and this same region is involved in hereditary renal carcinoma due to a 3;8 translocation. This region is also part of a larger deletion (3p14-23) characteristically associated with small cell carcinoma of the lung. Chromosome 3p14.2 is also the location of the most common constitutive fragile site which may be involved in the pathogensis of some of these rearrangements. We propose to construct precise restriction maps for two regions within the larger deleted region. The first region is from 3p14.1- p14.2 and the second is 3p21-p21.1. Using a chromosome 3p- specific cosmid library we will isolate sufficient cosmids to completely saturate these regions with at least 1 cosmid every 1000 kilobases. Unique sequence hybridization probes derived from the cosmids will be localized using a panel of somatic cell hybrids which define and span this region. Probes localized between 3p14.1-3p14.2 and 3p21-p21.1 will also be analyzed to find cosmids closest to several specific breakpoints. These will then form the start-point for the eventual cloning and characterization of these breakpoints. This work should facilitate the isolation of the critical regions involved in the pathogenesis of these diseases as well as setting the initiation the construction of a complete restriction map of this dynamic region of the genome.