DISTINCT 3P21.3 DELETIONS IN LUNG-CANCER AND IDENTIFICATION OF A NEW HUMAN SEMAPHORIN

Loss of chromosome 3p is a critical event in the pathogenesis of lung cancer. Overlapping homozygous 3p21.3 deletions in lung cancer cell li nes involving GNAI2 were characterized and found to involve a region o f genomic instability. A new widely expressed Semaphorin, H.SemaIV, wa s isolated from the GNAI2 deletion region. Reduced H.SemaIV expression allowed identification of additional cell lines with submicroscopic o r larger deletions of the locus which occurred in a heterogeneous mann er. We also demonstrate the presence of a distinct 3p21.3 homozygous d eletion region, adjacent to the DNA mismatch repair gene, hMLH1, and i dentified deletions in direct tumors. This appears to represent one of the first demonstrations of homozygous deletions affecting 3p in dire ct lung tumors.