Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization

Characteristic genetic changes underlying the metastatic progression of mal ignant melanoma is incompletely understood. The goal of our study was to ex plore specific chromosomal alterations associated with the aggressive behav ior of this neoplasm. Comparative genomic hybridization was performed to sc reen and compare genomic imbalances present in primary and metastatic melan omas. Sixteen primary and 12 metastatic specimens were analyzed. We found t hat the pattern of chromosomal aberrations is similar in the two subgroups; however, alterations present only in primary and/or metastatic tumors were also discovered. The mean number of genetic changes was 6.3 (range 1-14) i n primary and 7.8 (range 1-16) in metastatic lesions. Frequent losses invol ved 9p and 10q, Whereas gains most often occurred at 1q, 6p, 7q, and 8q. Di stinct, high-level amplifications were mapped to 1p12-p21 and 1p22-p31 in b oth tumor types. Amplification of 4q12-q13.1, 7q21.3-qter and 8q23-qter wer e detected only in primary tumors. The 20q13-qter amplicon was present in a metastatic tumor. The number of genetic alterations were significantly hig her in primary tumors which developed metastases within one year after the surgery compared to tumors without metastasis during this time period. Fluo rescence in situ hybridization with centromeric and locus-specific probes w as applied to validate CGH results on a subset of tumors. Comparison of FIS H and CGH data gave good correlation. The aggressive behavior of melanoma i s associated with accumulation of multiple genetic alterations. Chromosome regions, which differ in the primary and metastatic lesions, may represent potential targets to identify metastases-related chromosomal alterations. ( C) 2001 Wiley-Liss, Inc.