Exploring the mechanisms of long-term tumour evolution and genomic instability in marine transmissible cancers

Cancers are proliferative outgrowths of abnormal cells driven by a selfish evolutionary programme. Most cancers arise from and remain within the bodies of their respective host individuals. Rarely, however, cancers may escape their hosts to become ‘transmissible cancers’, infectious cell lineages that spread between individuals by direct transfer of cancer cells. As parasitic cancers capable of surviving for millennia, transmissible cancers offer a unique model for exploring how mutation, selection and cellular processes mould and constrain selfish tumour evolution.Marine bivalves (shellfish including clams, mussels and cockles) are affected by at least 10 transmissible cancers, which spread via waterborne cell transfer. The recurrent emergence of long-lived cancers in shellfish provides a valuable resource for comparative studies aiming to probe the basic mechanisms of tumour evolution, including extreme genomic instability. Yet, the evolutionary histories of these cancers are poorly understood.My vision is to elucidate the origins and evolution of marine transmissible cancers by conducting a large-scale comparative genomic study of these cancers. My aims are to:1. Understand how transmissible cancers arise, mutate and spread under the sea2. Identify the mechanisms and consequences of genomic instability in transmissible cancers.My research approach will involve:- Extensive tumour sampling across continents- Generation of high-quality bivalve genome assemblies- Application of state-of-the-art technologies, including laser microdissection and single-cell sequencing, to hundreds of tumours- Development of specialised methods for comparative cancer genome analysis.The intrinsic heterogeneity and short lifespans of most cancers may obscure their underlying biological patterns. By examining the convergent evolution of 10 long-lived cancers through a comparative-genomics lens, I intend to deliver fundamental insights into cancer biology and evolution.