Evidence for a Tumor Suppressor Gene Distal to BRCA1 in Prostate Cancer

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Abstract
The breast-ovarian cancer susceptibility gene, BRCA1, has been implicated by both epidemiologic and genetic studies to be involved in prostate cancer. We wished to test the frequency of BRCA1 deletion and that of other markers in the region of proximal 17q in prostate tumor cells. We used a dual-color fluorescence in situ hybridization (FISH) assay using P1 phage probes for the BRCA1 gene and 3 flanking sites at 17q12-21, as well as a chromosome 17 centromere-specific alpha-satellite probe, to detect deletions in single-cell suspensions and touch preparations from 23 primary clinical stage B prostate tumors and adjacent nontumor prostate tissues. Lymphoblastoid cells and prostate cells from a normal donor were used to determine control loss values. Significant loss (p less than 0.05) of at least 1 of the P1s was detected in 16 of 23 (70 percent) cases, and in 4 of those cases all markers were lost, consistent with whole chromosome loss. Of the 12 cases with subchromosomal loss, 8 had loss distal to BRCA1. Loss was detected in 5 cases previously reported by using allelic imbalance (AI) methodologies, and was detected in an additional 11 non-AI cases, suggesting that FISH is more sensitive than AI for deletion detection in prostate tumor cells. The data suggest that the region distal to BRCA1 may contain 1 or more prostate-specific tumor suppressor genes and that BRCA1 itself plays only a minor role in prostate cancer development.