ALLELIC IMBALANCE IN FAMILIAL AND SPORADIC PROSTATE-CANCER AT THE PUTATIVE HUMAN PROSTATE-CANCER SUSCEPTIBILITY LOCUS, HPC1

A recent report has provided strong evidence for a major prostate canc er susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 199 6). Most inherited cancer susceptibility genes function as tumour-supp ressor genes (TSGs). Allelic loss or imbalance in tumour tissue is oft en the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have valuated DMA from tissue obtain ed from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three marker s from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evide nce of allelic imbalance in only approximately 7.5% of informative tum ours. There was no difference between the familiar and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this gro up of patients, HPC1 is unlikely to be acting as a TSG in the developm ent of prostate cancer.