MAPPING OF A BREAST-CANCER TUMOR-SUPPRESSOR GENE LOCUS TO A 4-CM INTERVAL ON CHROMOSOME 18Q21

DPC4 and DCC, putative tumor suppressor genes implicated in the genesi s of several types of human cancer, lie on the long arm of human chrom osome 18. We examined 200 primary breast cancers for allelic losses on chromosome 18, using 15 microsatellite markers distributed along the long arm. Allelic loss was detected most frequently (29-30%) at loci m apped to 18q21. Deletion mapping of the 34 tumors showing partial or i nterstitial deletions identified a commonly deleted region within the 4-cM interval flanked by D18S474 and D18S487 at 18q21.1-q21.3. Althoug h this interval included the DPC4 and DCC genes, we excluded DPC4 from candidacy when polymerase chain reaction-single-strand conformation p olymorphism analysis of each exon failed to detect abnormalities in an y of the 54 breast cancers that exhibited loss of heterozygosity invol ving 18q. Allelic loss on 18q was found more frequently in tumors of t he solid tubular histological type (24 of 55, 44%) than in other types (24 of 113, 21%) (P = 0.0049). The results suggest that a tumor suppr essor gene located within the 4-cM region at 18q21, either DCC or anot her gene not yet identified, may play a role in the development of som e sporadic breast cancers, particularly those of the solid tubular typ e.