Localization of a tumor suppressor gene associated with the progression ofhuman breast carcinoma within a 1-cM interval of 8p22-p23.1

BACKGROUND, Frequent allelic losses on the short arm of chromosome 8 in sev eral types of human cancers, and deletion maps of this region in tumor DNAs , have suggested that 8p harbors one or more genes that are important for s uppressing tumorigenesis in the tissues in question. METHODS. To define the locations of potential tumor suppressor genes involv ed in breast carcinoma, the authors examined 144 primary breast carcinomas for loss of heterozygosity at 18 highly polymorphic microsatellite loci on 8p. They also sought correlations between allelic loss on 8p and several cl inicopathologic parameters. RESULTS. Allelic loss was observed in 74 of the 144 sporadic breast carcino mas examined. Whereas more than half of the informative tumors showed loss of an allele at every locus on the short arm, 32 showed partial or intersti tial deletions. Deletion mapping in this panel of tumors identified two dis tinct commonly deleted regions, one in a 1-cM interval flanked by D8S511 an d D8S1991 at 8p22-p23.1, and the other in a 16-cM interval flanked by D8S13 6 and D8S1477 at 8p22-p21. Allelic losses in both of these regions were obs erved more frequently in tumors of the solid-tubular or scirrhous type than in less aggressive histologic types. Furthermore, allelic loss in either r egion occurred more frequently in larger and infiltrative tumors (T1 < T2 < T3). CONCLUSIONS. The association of allelic losses on 8p with advanced tumor st age and aggressive histologic type implies that loss or inactivation of one of at least two putative tumor suppressor genes on 8p may contribute to th e progression of breast carcinoma. (C) 1999 American Cancer Society.