Recessive genetic mechanisms in the oncogenesis of prostatic carcinoma.
A detailed deletion mapping of a series of human prostatic carcinomas, using restriction fragment length polymorphism (RFLP) analysis of all chromosomes, showed allelic losses on individual chromosomes at variable frequencies. Allelic losses occurred on chromosomal arms 8p, 10pq, 16q and 18q in more than 30% of the cases. Losses of genetic information from one or two of the chromosomes 8, 10, or 16 were always present in tumors showing allelic losses, indicating that genes on these chromosomes have a central role in prostatic cancer. A more extensive study of these chromosomes was thus carried out and showed the highest frequency of allelic deletions to occur on the short arm of chromosome 8 (65%) (where the minimally deleted region was between the PLAT locus and pter). The long arm of chromosome 16 had allelic deletions in 56% of informative cases, with three different break points (the most distal being between D16S4 and D16S7). Chromosome 10 exhibited a complex deletion pattern, showing allelic losses from both the short (p) and the long (q) arms, evidence of non-reciprocal translocations of the q arm, and monosomy in some cases. Our data indicate that tumor suppressor genes involved in the oncogenesis of prostatic carcinoma may be localized between 8pter and the PLAT locus and that additional/alternative tumor suppressor gamma are likely to be localized on chromosome 10 and on the long arm of chromosome 16. More aggressive tumors were accompanied by a high or frequency of allelic losses.
Department of Urology, Karolinska Hospital, Stockholm, Sweden.
U S
US
Bergerheim
V P
VP
Collins
P
P
Ekman
K
K
Kunimi
D000483:Alleles; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm