Clonal Heterogeneity and Evolution in Primary Tumors and Metastases

Cancer is an evolutionary process driven by somatic mutations that accumulate in a population of cells. In principle, these mutations can be used as markers to infer the ancestral relationships between cells of a tumor, or to describe the patterns of cellular migrations between a primary tumor and metastases at distant anatomical sites. In practice, such analyses are complicated by the fact that bulk tumor samples are heterogeneous mixtures of cells, or clones. In this talk, I will describe approaches to study clonal heterogeneity and evolution using DNA sequencing data from bulk tumors. In particular, I will present methods to: infer seeding patterns of metastases and distinguish monoclonal vs. polyclonal seeding; identify copy number aberrations and whole-genome duplications in multi-sample sequencing data; study clonal evolution in longitudinal cancer sequencing data.