Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers

Prostate cancer Is one of the leading causes of cancer-related deaths for m en in the United States. Like other malignancies, prostate cancer is unders cored by a variety of aberrant genetic alterations during its development. Although loss of heterozygosity or allelic loss is frequently Identified am ong prostate cancers, few genes have been identified thus far as critical t o the development of invasive prostate cancers. in this report, we used the recently developed technology, the "differential subtraction chain," to pe rform a genome-wide search for sequences that are deleted in an aggressive prostate cancer. Among the deleted sequences, we found that one sequence wa s deleted in > 50% of prostate cancers we tested. We mapped this sequence t o chromosome 4q25 by screening the Genebridge 4 hamster radiation panel wit h primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin. Seque nce analysis indicates that myopodin shares significant homology with synap topodin, a protein closely associated with podocyte and neuron differentiat ion. Further study shows that frequent complete or partial deletions of the myopodin gene occurred among invasive prostate cancer cases (25 of 31 case s, or 80%). Statistical analysis indicates that deletion of myopodin is hig hly correlated with the invasiveness of prostate cancers, and thus may hold promise as an important prognostic marker for prostate cancers.