Liver metastatic ability of human melanoma cell line is associated with losses of chromosomes 4, 9p21-pter and 10p

Genetic changes underlying the aggressive progression of human cutaneous me lanoma are not completely understood. In order to characterise genetic alte rations associated with the metastatic behaviour of this neoplasm we used c omparative genomic hybridisation (CGH) in combination with fluorescence in situ hybridisation (FISH) on an experimental metastatic model of three rela ted human melanoma cell lines. Tumour lines were selected based on their va rious metastatic capacity to liver in immunosuppressed mice. The parental c ell line (A2058) was a human amelanotic melanoma cell line, adaptation of t his line to in vivo growth as xenograft the HT168 tumour and its cell line was established. After intrasplenic transplantation of HT168 cells into imm unosuppressed mice, a highly metastatic variant (HT168-M1) was selected. Se veral chromosomal aberrations common to all three lines indicating common c lonal origin, as well as additional non-shared chromosomal changes were fou nd. The original cell line (A2058) exhibited the highest number of genetic changes. Chromosomal alterations present only in the highly metastatic line (HT168-M1) involved losses on chromosome 4, 9p21.3-pter and 10p. Chromosom e copy number patterns and the nature of chromosome 4 loss were further inv estigated by FISH using different centromeric probes and a chromosome 4 pai nting probe. According to our CGH and FISH results we assume that alteratio ns present only in the aggressive metastatic subline are associated with th e increased - metastatic potential. Our observations further support the hy pothesis, based on some recently published data, that certain (so far unide ntified) suppressor genes having an important role in tumour progression ar e located on these chromosomes.