ALLELIC LOSS AND THE PROGRESSION OF BREAST-CANCER

To study genetic changes and the evolution of breast cancer, we assaye d for Loss of heterozygosity (LOH) in 12 sets of synchronous carcinoma in situ (CIS) and invasive cancer, compared to normal control DNA. Mi crosatellite markers were used, which map to each nonacrocentric autos omal arm. Eight tumor sets demonstrated LOH of the same allele in both concurrent invasive cancer and ductal CIS, for a total of 18 chromoso mal loci. Three of nine tumor sets showed LOH on 11p. In two of these sets, LOH was seen on 11p only in the invasive tumor, not the correspo nding CIS. One of these tumors also exhibited allelic loss in the inva sive tumor for 3 loci, all of which were retained in the noninvasive t umor. For two tumor sets, LOH was mirrored in matched ductal CIS, inva sive tumor, and lymph node metastasis. The maintenance of LOH for cert ain loci throughout the stages of breast cancer suggests clonality of the cancer cells.