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Comparison of DNA Gains and Losses in Primary Renal Clear Cell Carcinomas and Metastatic Sites: Importance of 1q and 3p Copy Number Changes in Metastatic Events¹

Institute of Human Genetics, University of Heidelberg, INF 328, 69120 Heidelberg, Germany [J. G., H. H-G., A. J., T. C.]; Department of Genetics and Pathology, Medical Academy of Szczecin, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland [J. G., P. H., J. L.]; Institute of Pathology, University of Witten Herdecke, Hausnerstr. 40, 42283 Wuppertal, Germany [S. S.]; and Institute of Pathology, University of Münster, Domagkstr. 17, 4400 Münster, Germany [C. B.]

Archival material from primary and metastatic renal clear cell carcinomas of 25 patients was studied by comparative genomic hybridization. Copy number changes of entire chromosomes or chromosomal subregions were detected in 22 primary and 21 metastatic tumors. Copy number changes affected the following chromosomes in at least 20% of the 25 primary tumors (minimal common region given in parentheses): gains were noted for chromosomes 1 (1q21q23), 5 (5q31q34), 7 (7p), 8 (8q), 16 (16p), 17 (17q12qter), 19, and 22 (22q12qter); losses were revealed for chromosomes 3 (3p21pter), 8 (8p23pter), 14 (14q21qter), and Y. The same chromosomal regions that were involved in primary renal clear cell carcinomas were also found in the respective metastatic tumors but with strikingly different frequencies for a few regions. Metastatic tumors showed a significantly higher frequency of complete or partial gains of the long arm of chromosome 1, in particular at 1q21q23 than primary tumors (16 cases versus 6 cases; P < 0.005). These data suggest a correlation of metastatic events in renal clear cell carcinomas with an increase in the copy number of genes located at 1q, in particular at 1q21q23. In contrast, the entire or partial loss of the short arm of chromosome 3 was significantly less frequent in metastatic tumors (8 cases versus 15 cases; P < 0.025). The validity of 1q and 3p copy number changes detected by comparative genomic hybridization was confirmed by interphase cytogenetics with region-specific yeast artificial chromosomes to paraffin-embedded tumor tissue sections.

¹ This study was supported by a grant from the Wilhelm-Sander Stiftung (to T. C. and S. S.). J. G. was supported by a stipend from the Deutscher Akademischer Austauschdienst.

² To whom requests for reprints should be addressed.

³ Present address: Institute of Anthropology and Human Genetics, Ludwig Maximilinans University, Richard Wagner Str. 10/I, D-80333 München, Germany.

Received 2/16/96. Accepted 12/ 2/96.

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