Transmissible cancer evolution and host interaction

Transmissible cancers are malignant somatic cell lineages that spread between individuals by the allogeneic transfer of living cancer cells. These cancers, whose three known instances in mammals affect dogs and Tasmanian devils, provide a unique perspective on cancer evolution and host interaction. I will investigate this by deeply sequencing whole genomes from 1100 tumours selected from across each cancer’s range, together with matched bulk RNA sequencing and targeted single-cell RNA sequencing. Time-resolved phylogenetic trees for each clone will be annotated with mutation and gene expression data, and the source and consequence of mutation explored. Host cell contribution to the tumour microenvironment, and its variation across hundreds of tumours, will be assessed using allelic and cell-type deconvolution. Combining genetic, microenvironment composition and clinical data, I will explain how the immunological interface between allogeneic cancer and host varies between individuals, and how this interaction controls the outcome of disease. The inherent heterogeneity and short lifespans of most cancers may obscure their underlying biological patterns. By capturing variation in hundreds of clonally derived tumours inhabiting different hosts, I seek to deeply probe the mutational, evolutionary and immunological principles of cancer.