CHROMOSOME BREAKPOINTS & RENAL & SMALL CELL LUNG CANCER

人类3号染色体的特定重排已经被证实是 特征性与恶性和发育相关 紊乱 染色体3 p14 -21区域的缺失是 自发性卵巢癌的恒定细胞遗传学特征 肾脏和这个相同的区域涉及遗传性肾 癌由于3;8易位。 该地区也是一个 一个较大的缺失（3 p14 -23）特征性地与小 肺细胞癌。 染色体3p14.2也是 最常见的组成性脆性部位的位置， 参与其中一些重排的发病机制。 我们建议为两个区域构建精确的限制性酶切图谱 在较大的删除区域内。 第一个区域来自3p14.1- p14.2，其次为3 p21-p21.1。 利用染色体3 p- 特异性粘粒文库，我们将分离足够的粘粒， 用至少1个粘粒完全饱和这些区域， 1000份。 独特序列杂交探针 将使用一组体细胞定位 定义并跨越该区域的杂交体。 探针定位 也将分析3p14.1-3p14.2和3 p21-p21.1之间的差异， 找到最接近几个特定断点的余弦。 这些将 然后形成最终克隆的起点， 这些断点的特征。 这项工作应有助于 分离出参与发病机制的关键区域， 这些疾病以及设置启动建设 基因组这个动态区域的完整限制性图谱。

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.