LOSS OF HETEROZYGOSITY AT CHROMOSOME 6Q CORRELATES WITH TUMOR PROGRESSION AND PATIENT SURVIVAL

Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast carcinoma and are thought to carry tumor suppressor genes. We have analysed human breast tumors with 9 polymorphic microsatellite markers that are specific to chromosome 6q. The mapping of smallest region of overlap (SRO) indicated location of candidate suppressor genes at 6q23 and 6q27. Variations in estrogen receptor (ER) expression were independent of the number of copies of the corresponding gene. Tumors with and without LOH on chromosome 6q were tested for association with clinicopathological factors. A significant association was found between LOH at 6q and the following: high S-phase, aneuploidy, deletions at chromosomes 3p and 9p and lower survival rate. In a multivariate model LOH at 6q is an independent prognostic variable and patients having tumors with LOH have approximately twofold increase in relative risk of death. It can be concluded that the 6q deletions give additional prognostic information that might be useful in breast cancer treatment.