CHROMOSOME BREAKPOINTS & RENAL & SMALL CELL LUNG CANCER

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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.