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Detection of Chromosome Aneuploidy in Interphase Nuclei from Human Primary Breast Tumors Using Chromosome-specific Repetitive DNA Probes¹

Departments of Human Genetics [P. D., T. K., R. K., P. L. P.] and Pathology [R. F. T., C. J. C.], University of Leiden, The Netherlands; Department of Pathology, University of Nijmegen, Nijmegen, The Netherlands [A. H. N. H.]; and Department of Medical Genetics, Toronto, Ontario, Canada [H. F. W.]

We have used in situ hybridization with chromosome specific repetitive DNA sequences as a probe to reveal particular chromosomes as distinct spots or clusters of signal within interphase nuclei. Using karyotypically defined cells and cell lines, we show that the number of signals obtained per nucleus correlates with the number of particular chromosomes present in that nucleus. Further, admixtures of karyotypically different cell lines could be detected. In situ hybridization of nuclei and metaphase spreads derived from the breast cancer cell line MCF-7 shows that a deviant number of spots/nucleus indicates a numerical and/or structural chromosomal aberration. In seven primary breast tumors studied, we detected numerical aberrations of the target sites of chromosomes 1 and/or 18. Although all had a single peak in DNA flow measurements, six of the cases appeared to be heterogeneous with respect to their spots/nucleus content.

¹ This work has been supported by the Royal Dutch Cancer Fund (Koningin Wilhelmina Fonds, IKW 86-15).

Received 1/15/88. Revised 6/10/88. Accepted 7/20/88.

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