503 BRAF-V600 Mutation discordance in Primary and Metastatic Melanoma

Abstract

Similar to other highly malignant tumors, melanoma is caused by the deregulation of multiple, interconnected intracellular pathways. These pathways often contain many genes mutated, deleted, amplified or epigenetically modified in a tumor and patient specific manner. Nowadays, different types of high throughput data (HTD) can be produced from tumor material to dissect these unique, patient specific set of deregulated genes. The complexity of these data led to the idea of approaching the analysis of cancer HTD from a network perspective. We have reconstructed a comprehensive regulatory network accounting for the pathways subverted in malignant melanoma. Published literature was manually reviewed and the quality of the reported biological data was assessed. This information was used to extract relevant genes and their known mutual interactions, which were integrated in a regulatory map. The current version of the cutaneous melanoma map contains 1127 molecular factors, including genes, mRNA, proteins, protein complexes, miRNAs, drugs and simple molecules. These molecular factors are interconnected through more than 1630 reactions. Furthermore, the map contains information about genes, proteins and miRNAs which are mutated, deleted, amplified or deregulated in expression in the context of malignant melanoma. The resulting oncogenic consequences on the signaling level and on the level of the cellular behavior are also part of the map. A special feature of our melanoma map represents the incorporation of drugs and their mode of action. The groups of drugs included range from medications approved for the treatment of malignant melanoma, drugs approved for the treatment of other cancer entities and pharmaceuticals in clinical trial. The melanoma map has been developed in a webplatform, which can be visualized, browsed and used for mining cell line or patient derived highthroughput data.