IDENTIFICATION OF HUMAN DAN GENE, MAPPING TO THE PUTATIVE NEUROBLASTOMA TUMOR-SUPPRESSOR LOCUS

The expression of DAN gene (previously designated as N03 gene) is sign ificantly reduced in a variety of transformed rat fibroblasts, includi ng v-src- (SR-3Y1), SV40- and v-mos-transformed 3Y1 cells, compared wi th that in parental 3Y1 cells. Recently, DAN gene has been shown to po ssess a tumor suppressive activity when it is overexpressed in SR-3Y1 cells (Ozaki & Sakiyama, 1994). To assess the involvement of DAN gene, vith human neoplasms, we have isolated human DAN counterpart from a no rmal lung cDNA library by using rat DAN cDNA as a probe, and determine d its chromosomal location. Human DAN gene mapped to chromosome 1p36.1 1-p36.13, which is well known to show highly significant linkage with the genesis and/or progression of human neuroblastoma. Southern blot a nalysis on tumor DNA from 26 patients with neuroblastoma has detected three patients showing genomic rearrangement or deletion within or clo sely linked to the DAN gene locus. Collectively, we propose that human DAN gene is a possible candidate for a tumor suppressor gene of human neuroblastoma.