Identification of new genes associated with melanoma.

PURPOSE: Repeated failures in melanoma therapy made clear that the molecular mechanisms leading to melanoma are still poorly understood. In this study, we aim to provide a more comprehensive understanding of the transcriptional profiles and signalling pathways associated with melanoma. METHODS: Gene expression was analysed using the Affymetrix Human Genome U133A 2.0 GeneChip arrays. To avoid culture artifacts, we used microdissected fresh frozen material of 18 melanocytic nevi (MN), 20 primary melanomas (PM) and 20 metastatic melanomas (MM). Statistical analysis was performed with Genomatix Chipinspector, Ingenuity™ Software, SPSS Software and Partek Genomic Suite 6.4. Expression levels of selected transcripts were verified by quantitative real-time RT-PCR and immunostaining of a tissue microarray sampling more than 280 cases of MN, PM and MM with known clinical outcome. RESULTS: A total of 284 differentially expressed genes was detected in PM compared with MN and 189 genes in MM compared with PM affecting common cancer pathways such as MAPK-, Wnt- and Notch-signalling. Using principal component analysis, the samples could be grouped according to their histological entity. We identified a panel of novel melanoma-associated markers: frizzled-related protein, an antagonist of Wnt; tranducin-like enhancer of split 1, a transcription factor partner of TCF/LEF-1; CNTN1, an activator of Notch signalling; two Serpin peptidase inhibitors, Serpin B3/B4 and the TGF-ß family member GDF15, the latter with association to MAPK-signalling.