CHROMOSOMAL GAINS AND LOSSES IN PRIMARY CUTANEOUS MELANOMAS DETECTED BY COMPARATIVE GENOMIC HYBRIDIZATION

The analysis of genetic changes in primary cutaneous melanoma has been limited by the need for fixation for diagnostic purposes. However, co mparative 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. T he analysis was performed on native, nonamplified DNA extracted from m anually dissected tumor sections. Loss of chromosome 9 was detected in 81% of the tumors, most commonly affecting the p arm. Additional comm on losses occurred on chromosomes 10 (63%), 6q (28%), and 8p (22%), Ga ins in copy number involved chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%), 20 (13%), 17 (13%), and 2 (13%). Amplifications indicating are as 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 an d vertical growth phase patterns. The overall pattern of regions affec ted by copy number changes is consistent with cytogenetic data from me tastatic melanoma; however, the frequencies of involvement differ, pro viding further insight into the course of genetic events.