title: DNA-methylation in C1R is a prognostic biomarker for acute myeloid leukemia.
abstract: BACKGROUND
  Epigenetic aberrations play a central role in the pathophysiology of acute myeloid leukemia (AML). It has been shown that molecular signatures based on DNA-methylation (DNAm) patterns can be used for classification of the disease. In this study, we followed the hypothesis that DNAm at a single CpG site might support risk stratification in AML.
  
  
  RESULTS
  Using DNAm profiles of 194 patients from The Cancer Genome Atlas (TCGA), we identified a CpG site in complement component 1 subcomponent R (C1R) as best suited biomarker: patients with higher methylation at this CpG site (>27 % DNAm) reveal significantly longer overall survival (53 versus 11 months; P < 0.0001). This finding was validated in an independent set of 62 DNAm profiles of cytogenetically normal AML patients (P = 0.009) and with a region-specific pyrosequencing assay in 84 AML samples (P = 0.012). DNAm of C1R correlated with genomic DNAm and gene expression patterns, whereas there was only moderate association with gene expression levels of C1R. These results indicate that DNAm of C1R is a biomarker reflecting chromatin reorganization rather than being of pathophysiological relevance per se. Notably, DNAm of C1R was associated with occurrence of specific genomic mutations that are traditionally used for risk stratification in AML. Furthermore, DNAm of C1R correlates also with overall survival in several other types of cancer, but the prognostic relevance was less pronounced than in AML.
  
  
  CONCLUSIONS
  Analysis of DNAm at C1R provides a simple, robust, and cost-effective biomarker to further complement risk assessment in AML.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Božić
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Frobel
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilop
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Jost
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
keywords: AML; Biomarker; C1R; DNA-methylation; Epigenetic; Leukemia; Prognosis; Survival; TCGA