GENETIC ALTERATIONS OF MICROSATELLITES ON CHROMOSOME-18 IN HUMAN BREAST-CARCINOMA

Allelic alterations of chromosome 18 microsatellites were determined u sing normal and tumor DNA pairs from 29 patients with infiltrating duc tal carcinoma of the breast. Loss of heterozygosity was detected in 62 % (18 of 29 patients) of the tumors at one or more of these microsatel lites. Eight of the 18 patients exhibited deletions in the region at 1 8q21.1. This chromosomal band is known to contain a tumor suppressor g ene (DCC) whose expression is frequently inactivated in several types of cancer. Ten other patients had deletions in regions not included in the DCC locus. Five of these patients revealed a common deletion at t he D18S50 locus (18q23), and the other five patients had deletions in various other regions of the chromosome. No apparent correlation betwe en loss of heterozygosity of chromosome 18 microsatellites and the cli nical stage was found in this series. The results indicate that, in ad dition to the DCC locus, the 18q123 region is likely to contain a seco nd tumor suppressor gene relevant to breast carcinogenesis. Four perce nt of all microsatellites tested in these patients showed allelic diff erences in the sizes of repeat units between tumor and the correspondi ng constitutional DNAs. The pattern of allele instability observed in breast carcinoma differed from that originally reported in a hereditar y type of colorectal carcinoma. The observation suggests that this phe nomenon is not a mechanism specific to neoplastic processes in breast carcinoma.