Sample processing obscures cancer-specific alterations in leukemic transcriptomes
Menée à l'aide d'échantillons sanguins prélevés sur des patients atteints d'une leucémie, cette étude met en évidence les effets des procédures de collecte d'échantillons sur l'activation de voies de signalisation spécifiques, ce qui est susceptible de produire des artéfacts dans les études génomiques
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-κB 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.
Proceedings of the National Academy of Sciences , article en libre accès, 2014