DELETION MAPPING AND LINKAGE ANALYSIS PROVIDE STRONG INDICATION FOR THE INVOLVEMENT OF THE HUMAN-CHROMOSOME REGION 8P12-P22 IN BREAST CARCINOGENESIS

We have identified a high frequency of loss of heterozygosity (LOH) on the human chromosome region 8p12-p22 in a panel of microdissected fam ilial (86% LOH) and sporadic (74% LOH) breast tumours. The two most fr equently deleted regions were defined around marker D8S133 and in a br oader centromeric region bounded by markers D8S137 and D8S339. We cann ot unequivocally characterize the 8p12-p22 loss as an early or a late event in breast carcinogenesis. in parallel, we have performed linkage analysis in four German breast cancer families. A location score grea ter than 13.67 corresponding to a LOD score of 2.97 at the marker D8S1 37 has been obtained. Our results considerably strengthen the evidence for a breast cancer susceptibility gene(s) located on the short arm o f the chromosome region at 8p12-p22.