Date: Thursday, February 5, 2026
Time: 1:00 pm
Location: EXP 610

Speaker: Dr. David Cheek (Harvard Medical School)

Title:  Age distinguishes selection from causation in cancer genomes.

Abstract:   Which mutations cause cancer? This question is central to understanding cancer biology and developing treatments. Towards answers, hundreds of thousands of cancer genomes have been sequenced, and signals of positive selection – excesses of functional relative to non-functional mutations – in cancer genomes have been detected across hundreds of genes. However, positive selection does not necessarily represent cancer causation, since positively selected mutations are pervasive in our normal aging tissues regardless of cancer development. To disentangle selection in normal tissue and causation of carcinogenesis, we propose a branching process model of somatic evolution, where cells stochastically divide, die, mutate, and transform to cancer. We derive an estimator for mutations’ effects on cancer risk based on a comparison of cancer and normal tissue genomes, which we apply to the blood, esophagus, and colon. We mathematically predict and empirically evidence that stronger cancer-causing mutations are enriched towards younger patient ages. This enables cancer-causing mutations to be identified from patient age distributions. We show moreover that the age-dependence of purported causal mutations in acute myeloid leukemia can be explained largely by normal blood evolution, contradicting the long-standing notion that childhood cancers require distinct mutations. Our probabilistic framework delineates carcinogenesis from normal tissue aging, improving the assessment of cancer risk conferred by mutations.

Biography: David Cheek is a Research Associate in Genetics at the Harvard Medical School working in the lab of Professor Kamila Naxerova. Dave is a mathematician with an undergraduate degree from Oxford University and a PhD from Edinburgh University. He is studying somatic evolution and carcinogenesis from a mathematical perspective. Outside the lab, he likes climbing and cold water swimming.
 
Google Scholar: https://scholar.google.com/citations?user=LueHiDMAAAAJ&hl=en