PHYSICAL MAPPING OF CHROMOSOME 8P22 MARKERS AND THEIR HOMOZYGOUS DELETION IN A METASTATIC PROSTATE-CANCER

Numerous studies have implicated the short arm of chromosome 8 as the site of one or more tumor suppressor genes inactivated in carcinogenes is of the prostate, colon, lung, and liver. Previously, we identified a homozygous deletion on chromosome 8p22 in a metastatic prostate canc er. To map this homozygous deletion physically, long-range restriction mapping was performed using yeast artificial chromosomes (YACs) spann ing approximately 2 Mb of chromosome band 8p22. Subcloned genomic DNA and cDNA probes isolated by hybrid capture from these YACs were mapped in relation to one another, reinforcing map integrity. Mapped single- copy probes from the region were then applied to DNA isolated from a m etastatic prostate cancer containing a chromosome 8p22 homozygous dele tion and indicated that its deletion spans 730-970 kb, Candidate genes PRLTS (PDGF-receptor beta-like tumor suppressor) and CTSB (cathepsin B) are located outside the region of homozygous deletion. Genethon mar ker D8S549 is located approximately at the center of this region of ho mozygous deletion. Two new microsatellite polymorphisms, D8S1991 and D 8S1992, also located within the region of homozygous deletion on chrom osome 8p22, are described. Physical mapping places cosmid CI8-2644 tel omeric to MSR (macrophage scavenger receptor), the reverse of a previo usly published map, altering the interpretation of published deletion studies. This work should prove helpful in the identification of candi date tumor suppressor genes in this region. (C) 1996 Academic Press, I nc.