IDENTIFICATION OF A ZINC-FINGER GENE AT 6Q25 - A CHROMOSOMAL REGION IMPLICATED IN DEVELOPMENT OF MANY SOLID TUMORS

We have used a rat model of epithelial ovarian cancer to identify a ge ne that shows decreased or lost expression in independently transforme d rat ovarian surface epithelial cell lines compared to the normal pro genitor cells, Hence, we refer to this gene as Lot-1 (Lost on transfor mation 1, GenBank accession no, U72620). Here, we report the cloning o f the likely human homologue and its initial characterization. The ded uced amino acid sequences of the cDNAs for rat and human LOT-1 (GenBan k accession no. U72621) contain seven zinc finger motifs of the C2H2 t ype as well as proline and glutamine rich areas. The genes share 76.4% identity at the nucleotide level, 67.7% at the amino acid level and 8 5.5% within the seven zinc finger motifs. LOT-1 is ubiquitously expres sed in normal human tissues but was not expressed in four of 11 (36%) human ovarian cancer cell lines or spontaneously transformed human ova rian surface epithelial cells, The human gene maps to chromosome 6 at band q25. We show that there is a 38% incidence of allelic loss at thi s chromosomal location in human ovarian cancers, This chromosomal regi on has also been implicated in the genesis of breast, kidney, and pleu ral mesothelial cancers, We suggest that this newly identified gene is not only of intrinsic interest as a ubiquitously expressed probable t ranscription factor but is a plausible candidate for the tumor suppres sor gene which likely resides in the region of chromosome 6 defined by band q25.