SOMATIC ALLELIC LOSS AT THE DCC, APC, NM23-H1 AND P53 TUMOR-SUPPRESSOR GENE LOCI IN HUMAN PROSTATIC-CARCINOMA

We present a restriction fragment length polymorphism (RFLP) analysis of 29 benign and 30 malignant prostatic tumors, using polymorphic DNA probes to the putative tumor suppressor genes DCC (Deleted in Colorect al Carcinoma; chromosome 18q21.3), nm23-H1 (17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53 (17p13). Six of 23 evaluable cancers (2 6%) showed loss of heterozygosity (LOH) at DCC; 5 were advanced stage and one was clinically localized (p < 0.05). Mapping 18q deletions, an other (advanced) cancer showed LOH at a locus distal to DCC (18q22), b ut no LOH at DCC. Three of 15 evaluable cancers (20%), all advanced, s howed LOH at APC. Three of eight (38%) cancers, of which 2 were advanc ed, showed LOH at p53. One high grade/stage cancer of 21 (5%) showed L OH at nm23-H1 (and also at DCC). Combining data, allelic losses at eit her DCC, APC, or p53 genes were seen in 13% of localized cancers, but in 71% of advanced cancers (p < 0.002). Allelic loss involving nm23-H1 is rare in prostatic carcinoma. We suggest that loss of tumor suppres sor genes DCC and/or an unidentified gene located distally on chromoso me 18q, APC, or p53 may influence progression in prostatic carcinoma.