Learn about the flu shot, COVID-19 vaccine, and our masking policy »
New to MyHealth?
Manage Your Care From Anywhere.
Access your health information from any device with MyHealth. You can message your clinic, view lab results, schedule an appointment, and pay your bill.
ALREADY HAVE AN ACCESS CODE?
DON'T HAVE AN ACCESS CODE?
NEED MORE DETAILS?
MyHealth for Mobile
Get the iPhone MyHealth app »
Get the Android MyHealth app »
Abstract
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 =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, ? = 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.
View details for DOI 10.1038/nm.3984
View details for PubMedID 26618723