Detection of invasion-related chromosomal changes in highly and weakly invasive melanoma cell clones by a modified comparative genomic hybridization approach

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Abstract
Invasion is a key step in the systemic spread of tumour cells. The aim of this study was to investigate whether specific chromosomal aberrations in melanoma occur during acquisition of a strongly invasive phenotype. We previously selected highly and weakly invasive cell clones from the human melanoma cell line Mel Im. Both cell clones retained a stable phenotype over more than 40 passages, revealing a five-fold difference in their invasive potential in vitro. Direct comparative genomic hybridization (CGH) (modified CGH) of the two cell clones was used as a powerful tool to screen for different chromosomal aberrations in both clones. Standard CGH and fluorescence in situ hybridization (FISH) was performed to verify the results of this improved technique. In general, the CGH pattern showed a high degree of identity consistent with the fact that the cell lines represent subclones of the same cell line. However, a few defined changes between the two cell clones were observed, including loss of 1q21-qter, 4q, 11p14-pter, 19q and 20p in the highly invasive cell clone. Two of the regions (1q and 11p) have already been suggested to be involved in melanoma progression, whereas changes in the others have not been detected before. In summary, our direct CGH approach proved to be suitable for fast and direct comparison of two cell types and allowed the identification of two known and three novel chromosomal changes involved in the acquisition of a strongly invasive melanoma cell phenotype.