title: Cancer heterogeneity and "the struggle for existence": diagnostic and analytical challenges.
abstract: The notions of inter- and intra-tumour heterogeneity (ITH) have been recognised for many years but recent advances in sequencing technology are allowing the true extent of both forms of heterogeneity to be revealed in detail for the first time. In this review we examine the current evidence for ITH, the possibility of cancers following a branched rather than linear evolutionary path and the potential implications both of these may have for the mechanisms of drug resistance acquisition. We also note that although clearly present in many cases, heterogeneity and branched evolution are not universal, with cases of tumour homogeneity and linear evolution still detected relatively frequently. The complexity induced by cases of ITH presents a considerable challenge for bioinformatics analyses and we illustrate this by describing the specific case of point mutation detection and a number of approaches which have been taken to combat these issues. Equally, the sequencing procedures which generate these data are rendered much more difficult in the face of ITH and we present a discussion of these problems in addition to describing some of the alternate paradigms being considered to overcome them.
authors.affiliation: Cancer Research UK London Research Institute, London, UK. Electronic address: stuart.horswell@cancer.org.uk.
authors.forename: Stuart
authors.initials: S
authors.lastname: Horswell
authors.forename: Nicholas
authors.initials: N
authors.lastname: Matthews
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D003627:Data Interpretation, Statistical; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D023281:Genomics / Q000379:methods* / Q000706:statistics & numerical data; D059014:High-Throughput Nucleotide Sequencing / Q000706:statistics & numerical data; D006801:Humans; D007621:Karyotyping; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017354:Point Mutation; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Bioinformatics; Cancer heterogeneity; Drug resistance; Next generation sequencing