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Access through your institution Buy or subscribe The Cancer Genome Atlas (TCGA) project has provided a wealth of data on tumour genetics, but generally with only a limited opportunity for

assessment of intratumour heterogeneity. The TCGA investigators analysed the 'tumour metagenome', comprising the genomes of all clones present, in only one sample per tumour; thus,

'deconvoluting' the data for individual clones is difficult — but not, as demonstrated by the results of a novel pan-cancer analysis, impossible. Maley, Andor, and colleagues

analysed TGCA data from 1,165 samples across 12 different cancer types using EXPANDS and a similar algorithm, PyClone. They found >80% of all the samples harboured at least two subclones,

and four on average. Importantly, the researchers found that intratumour genetic heterogeneity was universally associated with prognosis, but in a nonlinear fashion. Maley summarizes: “we

showed that, in two independent datasets, patients with either <25% or >75% of the tumour genomes affected by CNAs had improved survival compared with patients with intermediate levels

of CNAs. Similarly, patients with moderate levels of macroheterogeneity (3–4 subclones) had a worse prognosis than patients with fewer or more tumour subclones.” Interestingly,

morphological heterogeneity of tumour-cell nuclei was significantly correlated with genetic heterogeneity, and might, therefore, have clinical utility as a surrogate measure of genetic

diversity and/or prognosis. This is a preview of subscription content, access via your institution RELEVANT ARTICLES Open Access articles citing this article. * TUMOR CELL DENSITY DEPENDENT

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Li _Journal of Translational Medicine_ Open Access 17 March 2023 ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00

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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Andor, N. _ et al_. Pan-cancer analysis

of the extent and consequences of intratumor heterogeneity. _Nat. Med._ 10.1038/nm.3984 Download references Authors * David Killock View author publications You can also search for this

author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Killock, D. Intratumour heterogeneity — a game of snakes and ladders. _Nat

Rev Clin Oncol_ 13, 1 (2016). https://doi.org/10.1038/nrclinonc.2015.219 Download citation * Published: 15 December 2015 * Issue Date: January 2016 * DOI:

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