Transfer of chromosome 8 into two breast cancer cell lines: total exclusion of three regions indicates location of putative in vitro growth suppressor genes

Loss of heterozygosity (LOH) of the short arm of chromosome 8 occurs frequently in breast tumors. Fine mapping of the smallest regions of overlap of the deletions indicates that multiple tumor suppressor genes may be located in this region. We have performed microcell-mediated chromosome transfer of chromosome 8 into two breast cancer cell lines, 21MT-1 and T-47D. Twenty-two of the resulting hybrids were characterized extensively with chromosome 8 microsatellite markers and a subset were assayed for growth in vitro and soft agar clonicity. There was no evidence in any of the hybrids for suppression of growth or clonicity that could be attributed to the presence of particular regions of chromosome 8; however, none of the 22 hybrids examined had taken up all of the donor chromosome 8, and in fact there were three regions that contained only one allele of the markers genotyped in all 22 hybrids. These results are consistent with the presence of suppressor genes on the short arm of chromosome 8 causing strong growth suppression that is incompatible with growth in vitro; that is, multiple suppressor genes may exist on the short arm of chromosome 8.