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Division of Human Molecular Genetics, Department of Surgery [D. M. R., K. L. F., M. H., H. D-K.] and Department of Pathology [J. H. R.], Washington University, St. Louis, Missouri 63110, and Department of Pathology, St. Louis University, St. Louis, Missouri 63110 [N. J. P.]
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. Microsatellite 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 11p. In two of these sets, LOH was seen on 11p 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 retained 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.
1 Supported by a Veterans Administration RAG grant, an American Cancer Society Career Development Award, USARDC Grant DAMD-94-J-4293 (to D.M.R.), and by NIH Grants HG00469 and HG01066 (to H. D. K.).
2 To whom requests for reprints should be addressed, at 9901 Wohl Hospital, 660 South Euclid Avenue, St. Louis, MO 63110.
Received 8/30/95. Accepted 9/28/95.
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