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Open Access Green as soon as Postprint is submitted to ZB.
Pan-cancer analysis of the extent and consequences of intratumor heterogeneity.
J. Nat. Med. 22, 105-113 (2016)
Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect clones that are present at a â ‰1 10% frequency in 1,165 exome sequences from tumors in The Cancer Genome Atlas. 86% of tumors across 12 cancer types had at least two clones. ITH in the morphology of nuclei was associated with genetic ITH (Spearman's correlation coefficient, ρ = 0.24-0.41; P < 0.001). Mutation of a driver gene that typically appears in smaller clones was a survival risk factor (hazard ratio (HR) = 2.15, 95% confidence interval (CI): 1.71-2.69). The risk of mortality also increased when >2 clones coexisted in the same tumor sample (HR = 1.49, 95% CI: 1.20-1.87). In two independent data sets, copy-number alterations affecting either <25% or >75% of a tumor's genome predicted reduced risk (HR = 0.15, 95% CI: 0.08-0.29). Mortality risk also declined when >4 clones coexisted in the sample, suggesting a trade-off between the costs and benefits of genomic instability. ITH and genomic instability thus have the potential to be useful measures that can universally be applied to all cancers.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
1340-3443
e-ISSN
1861-0293
Journal
Journal of natural medicines
Quellenangaben
Volume: 22,
Issue: 1,
Pages: 105-113
Publisher
Springer
Publishing Place
Tokyo [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed