Abstract
Abstract: :
Purpose: Loss of chromosome 1p and chromosome 3 are related with metastatic disease and survival of Uveal Melanoma (UM) patients. The aim of this study was to examine whether the tumour suppressor genes, p73 and p63, located on chromosomes 1 and 3, respectively play a role in UM. Methods: Eleven UM cell lines, of which five were derived form primary tumours and six from metastases, were used as a model-system for UM. By fluorescent in situ hybridisation we determined loss of one or both alleles and expression levels of the genes were examined by RT-PCR. Protein levels were determined by Western blotting. Results: Although in some cell lines loss of p73 or p63 was observed, homozygous deletions were not found. Expression of the full-length p63 gene was observed in most of the cell lines and no expression of the p63 splice-variant with dominant-negative activity was observed. Expression of the full-length p73 gene was also observed in most cell lines, whereas the dominant negative isoform of p73 was expressed in only one of the primary-cell lines and half of the metastases-derived cell lines, but not in normal controls. Conclusion: The expression-pattern of the p63 gene appears to be normal in uveal melanoma cell lines but the pattern of the p73 isoform-expression is disturbed. This imbalance may play a role in tumour progression of UM.
Keywords: 464 melanoma • 420 genetics • 335 candidate gene analysis