Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 47, Pages 16802-16807Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1413374111
Keywords
leukemia; RNA splicing; nonsense-mediated decay; batch effects
Categories
Funding
- Damon Runyon Cancer Research Foundation [DFS 04-12]
- Ellison Medical Foundation [AG-NS-1030-13]
- NIH/National Cancer Institute (NCI) [P30 CA015704]
- Fred Hutchinson Cancer Research Center institutional funds
- NIH/NCI [T32 CA009657]
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Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and posttranscriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways; up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms; and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T-and B-cell activation, and NF-kappa B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors.
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