Allelic Loss and the Progression of Breast Cancer

To study genetic changes and the evolution of breast cancer, we assayed for loss of heterozygosity (LOH) in 12 sets of synchronous carcinoma in situ (CIS) and invasive cancer, compared to normal control DNA. Micro-satellite markers were used, which map to each nonacrocentric autosomal arm. Eight tumor sets demonstrated LOH of the same allele in both concurrent invasive cancer and ductal CIS, for a total of 18 chromosomal loci. Three of nine tumor sets showed LOH on Up. In two of these sets, LOH was seen on Up only in the invasive tumor, not the corresponding CIS. One of these tumors also exhibited allelic loss in the invasive tumor for 4 loci, all of which were retalned in the noninvasive tumor. For two tumor sets, LOH was mirrored in matched ductal CIS, invasive tumor, and lymph node metastasis. The maintenance of LOH for certain loci throughout the stages of breast cancer suggests clonality of the cancer cells.