title: Catch my drift? Making sense of genomic intra-tumour heterogeneity.
abstract: The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two components, the role of drift in cancer evolution has received little attention. Drift occurs when all individuals in the population have the same likelihood of producing surviving offspring, and so by definition a drifting population is one that is evolving neutrally. Here we focus on how neutral evolution is manifested in the cancer genome. We discuss how neutral passenger mutations provide a magnifying glass that reveals the evolutionary dynamics underpinning cancer development, and outline how statistical inference can be used to quantify these dynamics from sequencing data. We argue that only after we understand the impact of neutral drift on the genome can we begin to make full sense of clonal selection. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer? Edited by Dr. Robert A. Gatenby.
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, SM2 5NG, UK. Electronic address: andrea.sottoriva@icr.ac.uk.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sottoriva
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK. Electronic address: christopher.barnes@ucl.ac.uk.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Barnes
authors.affiliation: Evolution and Cancer Laboratory, Barts Cancer Institute, Charterhouse Sq, Queen Mary University of London, EC1M 6BQ, UK. Electronic address: t.graham@qmul.ac.uk.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Graham
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019143:Evolution, Molecular; D015972:Gene Expression Regulation, Neoplastic; D040961:Genetic Drift; D056084:Genetic Fitness; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D040941:Heredity; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: Clonal evolution of cancer; Clones; Intra-tumour heterogeneity; Neutral evolution; Next generation sequencing; Selection