Identification and characterization of proximal 6q deletions in prostate cancer

Allelic loss of 8p, 10q, 13q, 16q, and 18q has been frequently demonstrated in prostate cancer, implying the existence of putative tumor suppressor genes in these regions. However, there are likely a number of additional genetic events that define the progression from normal prostatic epithelium to prostate cancer that have yet to be identified. To characterize a novel region of deletion in sporadic prostate cancers, 52 tumors obtained from radical prostatectomy cases were analyzed for loss of heterozygosity (LOH) using 10 polymorphic markers spanning chromosome 6 including one marker on 6p and nine markers on 6q. Markers were selected from available databases, and a comprehensive linkage map was constructed. By this analysis, LOH for one or more polymorphic markers was detected in 17 of 52 sporadic prostate cancer cases (33%). Thirteen of 17 tumors were shown to have a common region of allelic loss extending from D6S286 to D6S283 or 6q14-21, with a minimum region of loss containing markers D6S1082 and D6S501. A second separate region of deletion centered around marker D6S404. LOH of one or more 6q markers did not correlate with Gleason grade or pathological stage of the cancer. In summary, this is the first comprehensive analysis of 6q deletions in prostate cancer, and we conclude that 6q14-21 may harbor a tumor suppressor gene important in prostate carcinogenesis.