Three distinct regions of allelic loss at 13q14, 13q21-22, and 13q33 in prostate cancer

Chromosome 13 is one of the most frequently altered chromosomes in cancer, including carcinoma of the prostate. Two known tumor suppressor genes, RE I and BRC42, map to chromosome 13; however, recent reports suggest that unkn own genes on 13q are more likely to be involved in the development of prost ate cancer. In order more fully to define the genetic changes on chromosome 13 in prostate neoplasms, we analyzed 27 polymorphic microsatellite marker s spanning the q arm for loss of heterozygosity in 40 primary tumors and in metastases from I I other patients who died of prostate cancer. Of the 40 primary tumors, 23 (58%) showed LOH for at least one marker. Three distinc regions at q14, q21-22, and q33, defined by markers D13S267 --> D13S153, D1 3S166 --> D13S1225, and D13S259 --> D13S274, showed the most frequent LOH, suggesting their involvement in the development of prostate cancer. I;or th e 12 patients whose rumors showed LOH at these markers, the average age at diagnosis was 58 years, which was younger than that (63 years, P < 0.05) fo r the 28 patients whose tumors lacked LOH. Ten of the 11 (91%) metastases s howed LOH with one or more markers. Two of the three most frequently delete d regions (i.e., q 14 and q2 1-22) in the primary tumors and markers linked to the RBI, BRCA2, and EDNRB genes showed high frequencies (56-71%) of LOH in metastases. These results demonstrate that allelic loss on chromosome 1 3 at q 14, q21-22, and q33 occurs in a subset of primary prostate tumors an d is a frequent event in metastatic lesions of prostate cancer. (C) 1999 Wi ley-Liss, Inc.