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Chromosomal Gains and Losses in Primary Cutaneous Melanomas Detected by Comparative Genomic Hybridization¹

Cancer Genetics Program, Cancer Center [B. C. B., D. P.] and Dermatopathology Section, Departments of Pathology and Dermatology [P. E. L.], University of California San Francisco, San Francisco, California 94143-0808, and Department of Dermatology, University of Würzburg, D-97080 Würzburg, Germany [B. C. B., H. H., E-B. B.]

The analysis of genetic changes in primary cutaneous melanoma has been limited by the need for fixation for diagnostic purposes. However, comparative genomic hybridization is able to analyze such specimens. We have applied comparative genomic hybridization to 32 primary melanomas to discover and map genomic regions with aberrant DNA copy numbers. The analysis was performed on native, nonamplified DNA extracted from manually dissected tumor sections. Loss of chromosome 9 was detected in 81% of the tumors, most commonly affecting the p arm. Additional common losses occurred on chromosomes 10 (63%), 6q (28%), and 8p (22%). Gains in copy number involved chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%), 20 (13%), 17 (13%), and 2 (13%). Amplifications indicating areas harboring potential oncogenes were seen at 4q12, 5p14.3-pter, 7q33-qter, 8q12–13, 11q13.3–14.2, and 17q25. Correlations among the regions with copy number changes indicate that losses of chromosomes 9 and 10 occur early on in melanoma progression, whereas gains of chromosome 7 occur later. This sequence of events was further substantiated by an intratumoral comparison of copy number changes in areas with radial and vertical growth phase patterns. The overall pattern of regions affected by copy number changes is consistent with cytogenetic data from metastatic melanoma; however, the frequencies of involvement differ, providing further insight into the course of genetic events.

¹ Supported by the Deutsche Forschungsgemeinschaft Grant Ba 794/2-1.

² To whom requests for reprints should be addressed, at Cancer Genetics Program, Cancer Center, University of California San Francisco, Box 0808, San Francisco, CA 94143-0808.

Received 11/12/97. Accepted 3/18/98.

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