Computational genomics and epigenomics to understand metastasis

What causes cancer cells to metastasise - cell migration from the primary tumour and growth in other organs - is unknown. Surprisingly, comparison of the genomes of metastases to primary tumours has generally failed to identify any metastasis driver mutations, and our hypothesis to explain this is two-fold: (1) that epigenetic changes (DNA methylation and chromatin changes) have a key role in enabling metastasis, and (2) that the complexity of the metastasis evolutionary dynamics has meant that genetic metastasis drivers have been missed. In this project, we will develop a computational framework that enables the robust identification genetic and epigenetic drivers of metastasis. The framework will be based on stochastic mathematical models of cancer evolution. The framework will be applied to an existing large multi-omic multi-region sequencing dataset to identify drivers of colorectal cancer metastasis.