Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization.
Characteristic genetic changes underlying the metastatic progression of malignant melanoma is incompletely understood. The goal of our study was to explore specific chromosomal alterations associated with the aggressive behavior of this neoplasm. Comparative genomic hybridization was performed to screen and compare genomic imbalances present in primary and metastatic melanomas. Sixteen primary and 12 metastatic specimens were analyzed. We found that 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) in primary and 7.8 (range 1-16) in metastatic lesions. Frequent losses involved 9p and 10q, whereas gains most often occurred at 1q, 6p, 7q, and 8q. Distinct, high-level amplifications were mapped to 1p12-p21 and 1p22-p31 in both tumor types. Amplification of 4q12-q13.1, 7q21.3-qter and 8q23-qter were detected only in primary tumors. The 20q13-qter amplicon was present in a metastatic tumor. The number of genetic alterations were significantly higher in primary tumors which developed metastases within one year after the surgery compared to tumors without metastasis during this time period. Fluorescence in situ hybridization with centromeric and locus-specific probes was applied to validate CGH results on a subset of tumors. Comparison of FISH and CGH data gave good correlation. The aggressive behavior of melanoma is 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.
Balázs
M
M
Medical and Health Science Center, School of Public Health, Department of Preventive Medicine, University of Debrecen, H-4032 Debrecen, Nagyerdei krt. 98, Hungary. margo@jaguar.dote.hu
Adám
Z
Z
Treszl
A
A
Bégány A
Hunyadi
J
J
Adány
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D020223:Chromosome Painting; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007621:Karyotyping; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm