DISTINCT REGIONS OF ALLELIC LOSS ON 13Q IN PROSTATE-CANCER

Loss of heterozygosity (LOH) involving the long arm of chromosome 13 h as been reported to occur in as many as one third of primary prostate cancers, Candidate tumor suppressor genes on 13q that may be important in the development of prostate cancer include the retinoblastoma susc eptibility gene (RB1) and a gene associated with inherited breast canc er (BRCA2). To define the pattern of allelic loss of 13q in prostate c ancer, LOH analysis was performed using nine mapped polymorphic marker s spanning the entire chromosomal arm, Nineteen (48%) of 40 prostate c ancer cases obtained following radical prostatectomy demonstrated alle lic loss with at least one marker, Furthermore, 13 (33%) of 40 cases h ad evidence of allelic loss involving a region of 13q14 containing RB1 , To test the hypothesis that RB1 is the targeted tumor suppressor gen e in this region, 37 of 40 cases were assessed for expression of pRB, the protein product of RB1 using immunohistochemical techniques, By th is analysis, 8 (22%) of 37 prostate tumors demonstrated no pRB express ion, However, allelic loss at RB1, assessed with an intragenic marker, did not correlate with absent pRB expression (Fisher's exact test, P = 0.375), Taken together, these data confirm that allelic loss of a co mmon region of 13q14 occurs in approximately one third of prostate can cers, Lack of correlation of LOH at RB1 with absent pRB expression sug gests the existence of another tumor suppressor gene in this region im portant in prostate cancer.