title: Tumor evolution: Linear, branching, neutral or punctuated?
abstract: Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients. Furthermore, emerging evidence suggests that models may change during tumor progression or operate concurrently for different classes of mutations. Finally, we discuss data that supports the theory that most human tumors evolve from a single cell in the normal tissue. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Davis
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ruli
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: nnavin@mdanderson.org.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Navin
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; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D016014:Linear Models; 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: Cancer biology; Cancer genomics; Genome evolution; Intratumor heterogeneity; Single cell genomics; Tumor evolution