Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients

Research output: Contribution to journalArticle

Abstract

Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.

Details

Authors
  • Nicolas Rapin
  • Frederik Otzen Bagger
  • Johan Jendholm
  • Helena Mora-Jensen
  • Anders Krogh
  • Alexander Kohlmann
  • Christian Thiede
  • Niels Borregaard
  • Lars Bullinger
  • Ole Winther
  • Kim Theilgaard-Moench
  • Bo T. Porse
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)894-904
JournalBlood
Volume123
Issue number6
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes