Sample Processing Obscures Cancer-Specific Alterations in Leukemic Transcriptomes

Strategic Insights -

Researchers from the University of Washington have discovered that standard blood collection procedures can rapidly change the transcriptional and posttranscriptional landscapes of hematopoietic cells, leading to biased activation of specific biological pathways. This study highlights the potential confounding effects of technical artifacts in cancer genomics data and emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. The researchers found that affected genes include common mutational targets and thousands of other genes participating in various biological processes.

Key Takeaways:

  • Standard blood collection procedures can rapidly change the transcriptional and posttranscriptional landscapes of hematopoietic cells, leading to biased activation of specific biological pathways.
  • The 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 incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes.
  • Keeping blood on ice markedly reduces changes to the transcriptome.
  • The study identified biomarkers that detect prolonged incubation of individual samples.
  • The researchers found that sample processing effects are particularly evident in pan-cancer analyses.
  • The study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors.

Statistics:

  • Up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes can be explained by incubation-induced dysregulation.
  • The majority of published leukemic transcriptomes exhibit signals of incubation-induced dysregulation.
  • Thousands of genes participating in various biological processes are affected by standard blood collection procedures.
  • The identified biomarkers can detect prolonged incubation of individual samples.

Sources:

  • Proceedings of the National Academy of Sciences of the United States of America, 2014;111(47):16802-16807
  • Natl Acad Sciences, 2101 Constitution Ave NW, Washington, DC 20418, USA