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Increased Copy Number at 20q13 in Breast Cancer: Defining the Critical Region and Exclusion of Candidate Genes¹

Laboratory of Cancer Genetics, Department of Laboratory Medicine, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere [M. M. T., M. T., A. K., R. K., O-P. K.]; Department of Biomedical Sciences, University of Tampere, P.O. Box 607, FIN-33101 Tampere [M. M. T., A. K., J. J. I.], Finland; Lawrence Berkeley Laboratory, Berkeley, California 94720 [C. C., D. K., F. S., J. W. G.]; and Division of Molecular Cytometry, Department of Laboratory Medicine, University of California, San Francisco, California 94143-0808 [T. S., M. H., W-L. K., F. M. W., J. W. G.]

Studies by comparative genomic hybridization have indicated that a major new locus for DNA amplification in breast cancer is 20q13 and suggested that this genetic event is associated with aggressive clinical behavior. We used interphase fluorescence in situ hybridization with anonymous cosmid probes and gene-specific P1 clones to determine the minimal common region of increased copy number and to study involvement of known genes at 20q13. Based on high-level copy number increases (3 to 10-fold) found with one or more probes in 5 of 14 (35%) breast cancer cell lines and in 3 of 36 (8%) primary tumors, the critical region was narrowed to 1.5 megabases at 20q13.2 defined by fractional length pter values 0.81–0.84. Previously known genes were excluded as candidates, implying that this chromosomal region harbors a novel oncogene that contributes to the malignant progression of breast cancer.

¹ This study was supported by the Finnish Science Academy, Finnish Cancer Society, Sigrid Juselius Foundation, Reino Lahtikari Foundation, NIH Grants CA528207 and CA44768, Department of Energy Contracts DE-AC-03-76SF00098, W-7405-ENG-48, W-7405-ENG-36, and Imagenetics, Inc.

² Supported by the Finnish Cultural Foundation, Pirkanmaa Cancer Society, and Emil Aaltonen Foundation.

³ Supported by the Finnish Cancer Society.

⁴ To whom requests for reprints should be addressed.

Received 5/27/94. Accepted 7/ 5/94.

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