The PISSLRE gene: Structure, exon skipping, and exclusion as tumor suppressor in breast cancer

In sporadic breast cancer, loss of heterozygosity (LOH) frequently occurs i n three discrete regions of the long arm of chromosome 16q, the most telome ric of which is located at 16q24.3. Among the genes mapped to this region, PISSLRE is a plausible candidate tumor suppressor gene. It codes for a puta tive cyclin-dependent kinase that, as with other members of this family, is likely to be involved in regulating the cell cycle and therefore may have a role in oncogenesis. We characterized the genomic structure of PISSLRE an d found that the splicing of this gene is complex. A variety of different t ranscripts were identified, including those due to cryptic splice sites, ex on skipping, insertion of intronic sequences, and exon scrambling. The last phenomenon was observed in a rare PISSLRE transcript in which exons are jo ined at a nonconsensus splice site in an order different from that predicte d by the genomic sequence. To screen the PISSLRE gene in breast tumors with ascertained LOH at 16q24-.3, we have analyzed each exon by single-strand c onformational polymorphism. No variation was found in the coding sequence, leading us to conclude that another tumor suppressor must be targeted by LO H in sporadic breast cancer. (C) 1999 Academic Press.