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Frequent Alteration of the DF3 Tumor-associated Antigen Gene in Primary Human Breast Carcinomas¹

Laboratory of Tumor Immunology and Biology, NCI, NIH, Bethesda, Maryland 20892 [G. R. M., C. S. C., D. S. L., R. C.]; Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 [J. S., D. W. K.]; Centre Renè Huguenin, 5 rue Gaston Latouche, 92211 St. Cloud, France [R. L.]

The gene for the human DF3 breast carcinoma-associated antigen contains a conserved (G+C)-rich 60-base pair tandem repeat and maps to chromosome 1q21-24. In the present study we isolated and characterized 1220 base pairs of nonrepetitive adjacent sequences. Multiple alleles were identified by fragment size. Signal intensity of hybrids with the tandem and unique sequence probes indicated that allelic variation is due to different numbers of repeats. Probes for both the tandem and the unique sequences were used to study the DF3 locus in human breast tumor DNAs. Seventy of 110 breast tumor DNAs were informative at the DF3 locus. Of these, 20 (29%) showed a loss of heterozygosity, while eight (11%) had an increased copy number of one allele. In some cases, the loss of heterozygosity or increased copy number did not extend to other markers on chromosome 1q or 1p. These data indicate that the chromosomal region around the DF3 locus is affected by mutations at high frequency.

¹ This investigation was supported in part by USPHS Grant CA-38869 from the National Cancer Institute, DHHS, and by a Burroughs Wellcome Award in Clinical Pharmacology (D. W. K.).

² Present address: Servizio Anatomia Pathologica, USL-1, Via Cavour 31, 10132 Torino, Italy.

³ To whom requests for reprints should be addressed, at Dana-Farber Cancer Institute, Division of Medicine, 44 Binney Street, Boston, MA 02115.

Received 5/24/89. Revised 9/18/89. Accepted 9/21/89.