title: Inferring mutational timing and reconstructing tumour evolutionary histories.
abstract: Cancer evolution can be considered within a Darwinian framework. Both micro and macro-evolutionary theories can be applied to understand tumour progression and treatment failure. Owing to cancers' complexity and heterogeneity the rules of tumour evolution, such as the role of selection, remain incompletely understood. The timing of mutational events during tumour evolution presents diagnostic, prognostic and therapeutic opportunities. Here we review the current sampling and computational approaches for inferring mutational timing and the evidence from next generation sequencing-informed data on mutational timing across all tumour types. We discuss how this knowledge can be used to illuminate the genes and pathways that drive cancer initiation and relapse; and to support drug development and clinical trial design.
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Samra
authors.initials: S
authors.lastname: Turajlic
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: McGranahan
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK; UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, Huntley Street, WC1E 6DD, UK. Electronic address: Charles.swanton@crick.ac.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D019143:Evolution, Molecular; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D059645:Mutation Rate; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics
keywords: Cancer evolution; Intratumour heterogeneity; Mutational timing; Subclonal mutations; Treatment resistance