8pter-p23 deletion is associated with racial differences in prostate cancer outcome

Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of ch romosome 8, 8pter-p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter-p23 region may be correlat ed with poor prognosis. The aim of the present study was to physically defi ne the minimal region of 8pter-p23 deletion and to define the frequency and prognostic significance of 8pter-p23 loss in human prostate tumors, DNA wa s purified from normal and tumor tissues of 45 radical prostatectomy specim ens and amplified for 15 highly polymorphic microsatellite sequences, 13 sp anning 8pter-p23 and 2 proximal 8p markers. Allelic loss of 8p sequences wa s observed in 28 of 45 (62%) tumors examined, Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter-p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264- D8S1824-D8S1781-D8S262-D8S1798, When serum prostate-specific antigen was us ed as a surrogate end point marker for survival, 8pter-p23 loss was signifi cantly associated with reduced disease-free progression (log-rank P = 0.042 6). Moreover, loss of the 8pter-p23 region was significantly associated wit h poor survival for American Caucasian (log-rank P = 0.0024) but not Africa n-American (log-rank P = 0.5832) prostate cancer patients. These studies su ggest that independent deletion of 8pter-p23 is differentially associated w ith disease recurrence and poor outcome in American Caucasian but not Afric an-American prostate cancer patients.