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Phylogenetics of Cancer 2
Quantitative measurement of cancer evolutionary history from single-sample bulk DNA methylation data
Cancers evolve. Current methods to measure evolutionary dynamics rely on genome sequencing of multiple samples from each tumour to detect subclonal mutations and using them to perform phylogenetic tree inference. In this talk I will show a very different approach that uses only single-sample bulk DNA methylation data to provide an unexpectedly rich read out of the clonal history of tumour evolution. Our approach relies on “fluctuating DNA methylation” - the random loss and gain of methylation at particular CpG sites which are evolutionarily neutral. We infer evolutionary history by modelling the site frequency spectrum of fluctuating methylation within single samples. I will show applications in haematological cancers where we use the approach to measure, in 1000s of cancers, tumour age, growth rate and various features of subclonal dynamics.