Definitive functional evidence for a tumor suppressor gene on human chromosome 7q31.1 neighboring the Fra7G site

We have previously shown that loss of heterozygosity (LOH) on human chromos ome (hchr) 7 at q31.1 is common in a variety of tumors of epithelial origin . Frequent LOH of a specific chromosomal marker is indicative of a closely linked tumor suppressor gene (TSG). However, recent reports have also indic ated that such a high frequency of LOH could be due to the presence in this region of the second most common aphidicolin-inducible fragile site in the human genome (Fra7G), To address this controversy, we introduced single co pies of hchr7 or hchr12 into a highly aggressive human prostate carcinoma c ell line (PC3) by microcell-mediated transfer. The tumorigenicity of six cl ones of PC3/hchr7 hybrids and three clones of PCRhchr12 hybrids, obtained i n four separate fusion experiments, were studied in BALB/c nude mice. All b ut one of the PC3/hchr7 hybrids increased tumor latency by at least twofold , whereas none of the PC3/hchr12 hybrids delayed tumor onset. No difference s in the in vitro growth rate Here observed among any of the cell lines ass ayed (parental and hybrids) suggesting that the observed tumor suppression was due to factors other than cell cycle regulation. Deletion mapping of th e PC3/hchr7 tumors obtained after reversion to the malignant phenotype reve aled a common region of loss centred around 7q31.1, supporting the TSG hypo thesis. The smallest commonly deleted region was similar to 1.5 Mb in size and flanked by the markers D7S486 and D7S655.