DETAILED DELETION MAPPING OF CHROMOSOME ARM 3P IN BREAST CANCERS - A 2-CM REGION ON 3P14.3-21.1 AND A 5-CM REGION ON 3P24.3-25.1 COMMONLY DELETED IN TUMORS

Loss of heterozygosity (LOH) on 3p is frequent in human renal cell car cinomas, lung cancers, and breast cancers. To define the region(s) on 3p that harbor presumptive tumor suppressor gene(s) for breast cancer, we examined 196 primary breast tumors for their patterns of LOH at 22 microsatellite marker loci distributed along this chromosome arm. All elic loss at one or more loci was observed in 101 (52%) of these tumor s. Detailed deletion mapping identified two distinct commonly deleted regions; one was localized to a 2-cM interval flanked by D3S1547 and D 3S1295 at 3p14.3-21.1, and the other to a 5-cM interval flanked by D3S 1286 and D3S1585 at 3p24.3-25.1. The FHIT gene lies in the vicinity of the proximal commonly deleted region. Attempts to correlate LOH on 3p to clinicopathological parameters detected an association with the ab sence of the progesterone receptor (P = 0.0096). The results suggest t hat inactivation of unidentified tumor suppressor genes on 3p plays a role in the mechanism whereby hormone dependency is lost in the course of breast carcinogenesis. (C) 1997 Wiley-Liss, Inc.