Transformed melanocytes use several strategies to enable their progression to advanced melanoma and metastasis, including genetic and epigenetic alterations, along with disruptions to gene and protein expression. This consortium aims to identify novel biomarkers for predicting the progression and prognosis of melanoma. To achieve this, a concerted collaborative effort is proposed here between key academic and industrial partners, centred on intersectorial training of experienced researchers. Our first goal is to identify novel methylated genes via several complementary screening methods, followed by validation extensive melanoma cohorts available to the consortium. We will use the following strategies to identify methylated genes: (1) an array-based technique called MeDIP-ON-CHIP, (2) a high-throughput bisulphite-based technique developed by Illumina (to simultaneously analyse up to 800 genes over 96 samples) and (3) in silico analysis of DNA microarray data. To validate these methylation targets, we will use both qualitative and quantitative methylation-specific PCR (MSP) and determine if these methylation events correlate with melanoma progression, i.e. from benign and atypical nevi to primary and metastatic tumours. Our second goal is to validate genes that associate with melanoma progression and prognosis. For this aspect of the project, we will concentrate on the application of tissue microarray technology and associated image analysis approaches to validate molecular determinants of melanoma progression. Prioritised targets will then be functionally validated by a unique in vitro assay that models extravasation, or exit of cancer cells out of the blood stream, a key step in the metastatic process. Overall, these studies will give clues to melanoma progression, and may identify important targets for melanoma treatment. In addition, this industry-academic partnership will provide a valuable cross-disciplinary training ground for emerging researchers.
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Funding SchemeMC-IAPP - Industry-Academia Partnerships and Pathways (IAPP)