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 Colorectal Carcinoma; chromosome 18q21.3), nm23-H1 (17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53 (17p13). Six of 23 evaluable cancers (26%) showed loss of heterozygosity (LOH) at DCC; 5 were advanced stage and one was clinically localized (p < 0.05). Mapping 18q deletions, another (advanced) cancer showed LOH at a locus distal to DCC (18q22), but no LOH at DCC. Three of 15 evaluable cancers (20%), all advanced, showed LOH at APC. Three of eight (38%) cancers, of which 2 were advanced, showed LOH at p53. One high grade/stage cancer of 21 (5%) showed LOH at nm23-H1 (and also at DCC). Combining data, allelic losses at either 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 suppressor genes DCC and/or an unidentified gene located distally on chromosome 18q, APC, or p53 may influence progression in prostatic carcinoma.
Brewster
S F
SF
Department of Urology, Southmead Hospital, Bristol, United Kingdom.
Browne
S
S
Brown
K W
KW
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000483:Alleles; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002895:Chromosomes, Human, Pair 5; D015342:DNA Probes; D017491:Genes, APC / Q000235:genetics*; D016163:Genes, DCC / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D012150:Polymorphism, Restriction Fragment Length; D011470:Prostatic Hyperplasia / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D015342:DNA Probes; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins