Differentially expressed genes during human cutaneous melanocytic tumor progression : a focus on cancer/testis-associated genes

Human cutaneous melanoma, the skin cancer originating from the pigment producing melanocyte, is one of the most aggressive types of tumors due to its early dissemination. The progression of melanoma surpasses several stages from common nevi to metastatic tumors. For diagnostic and clinical purposes it is crucial to have a set of marker genes that can distinguish between these different stages of melanocytic tumor progression. Using mRNA differential display and suppression subtractive hybridization we compared expression profiles of melanocytic samples with different metastatic capacities. With these technique we detected several differentially expressed genes. Two of these were novel members of the growing family of cancer/testis-associated genes (CTAs): SPAN-Xc and XAGE-1b. Expression of these genes is restricted to germ cells (and precursors) and cancerous cells.The putative proteins of XAGE-1b and SPAN-Xc share many features. Next to their nuclear localization they both are highly charged proteins encode by X-chromosome linked genes. Their characteristic expression patterns qualify CTAs as candidate antigens for anti-tumor immunotherapeutic strategies. We compared the expression profiles of three melanoma differentiation antigens with those of eight CTAs in melanoma metastases. These data show that CTAs can indeed increase the number of lesions positive for putative target antigens in immunotherapy. The last chapter of this thesis discusses the known and putative functions of various CTAs in testis and cancer. Many of them seem to have a role in transcriptional and cell cycle regulation. Preliminary results on putative interactants of XAGE-1b and SPAN-Xc point to a possible role in telomere-associated functions. In conclusion, CTA expression in tumors may be the result of an aberrant activation of testis-specific genes. Unraveling the functional role of CTAs and their possible use in immunotherapy against tumors depends on future in-depth studies. Such efforts may clarify the link CTAs seem to represent between gametogenesis and tumorigenesis