5 DISTINCT DELETED REGIONS ON CHROMOSOME-17 DEFINING DIFFERENT SUBSETS OF HUMAN PRIMARY BREAST-TUMORS

In this study, we analyzed 105 paired sporadic primary breast tumor an d normal tissue samples for loss of heterozygosity (LOH) on chromosome 17, using 12 polymorphic markers. We have identified partial or inter stitial LOH in five separate regions of chromosome 17. Two of the dele ted regions lie on the short arm of the chromosome, the first (region I, D17S5) in the telomeric part, distal to TP53 and the second spannin g the TP53 gene (region II). Three of the five deleted regions lie on the long arm of chromosome 17: region III, on the proximal long arm be tween D17S250 and THRA1; region IV, between D17S776 and D17S579, inclu ding the BRCA1 gene, and region V, located distal to D17S733. No stati stically significant correlations were observed between clinicopatholo gical characteristics or steroid hormone receptor status and deletion of either region I or II. However, patients whose tumors had LOH for r egion I showed relapse or death more frequently than patients with tum ors informative for this region but without LOH (p = 0.002). Statistic ally significant correlations between LOH at each of the three deleted regions of 17q and a high mitotic index were observed (region III, p = 0.005; region IV, p = 0.02, and region V, p = 0.004). In addition, L OH at region IV showed a significant association with paucity of estro gen receptors (p = 0.01). Our results show a complex pattern of LOH on chromosome 17 in breast cancer and a correlation of these events with different clinical parameters. This pattern suggests that particular subsets of allele loss may contribute specifically to different clinic ally defined subsets of sporadic breast tumors.