INTEGRATED YAC CONTIG CONTAINING THE 3P14.2 HEREDITARY RENAL-CARCINOMA 3-8-TRANSLOCATION BREAKPOINT AND THE FRAGILE SITE FRA3B

An extended YAC contig has been developed for the 3p14 region containi ng the hereditary renal carcinoma 3;8 translocation breakpoint and the 3p14.2 fragile site FRA3B. This region of chromosome 3 has been impli cated by chromosomal translocation, deletion, and loss of heterozygosi ty in the pathogenesis of several malignant diseases. The contig allow s accurate positioning of candidate genes, polymorphic markers, and ot her 3p rearrangements within this region. The contig, spanning approxi mately 6 Mb of DNA, contains 51 YACs identified by 27 markers, includi ng a subset of CA repeats located in the 3p14.1-14.2 interval. The ord er of CA microsatellites, derived from marker content of the YACs, is in agreement with the order previously determined by genetic linkage s tudies. We find that the protein-tyrosine phosphatase gamma gene, PTPR G, is located minimally 1 Mb proximal to the t(3;8) breakpoint. The mo re proximal 3p homozygous deletion in the small-cell lung cancer cell line, U2020, is more than 5 Mb from the site of the 3;8 translocation. This integrated physical and genetic map provides a framework for fur ther investigations of malignant diseases associated with proximal 3p loss. In addition, the positioning of separate 3p14.2 aphidicolin-indu ced breakpoints suggests that FRA3B may represent a region rather than a single site. (C) 1994 Wiley-Liss, Inc.