title: Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks.
abstract: Chronic lymphocytic leukaemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, here we present genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients measured by the ATAC-seq assay. We also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting data set, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status-which distinguishes the two major subtypes of CLL-was accurately predicted by the chromatin profiles and gene regulatory networks inferred for IGHV-mutated versus IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukaemia and demonstrated the feasibility of large-scale chromatin accessibility mapping in cancer cohorts and clinical research.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: André F
authors.initials: AF
authors.lastname: Rendeiro
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidl
authors.affiliation: Faculty of Medicine, Cancer Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Jonathan C
authors.identifier: 0000-0002-0972-2881
authors.initials: JC
authors.lastname: Strefford
authors.affiliation: Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK.
authors.forename: Renata
authors.initials: R
authors.lastname: Walewska
authors.affiliation: Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK.
authors.forename: Zadie
authors.initials: Z
authors.lastname: Davis
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Farlik
authors.affiliation: Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK.
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.|Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.|Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
authors.forename: Christoph
authors.identifier: 0000-0001-6091-3088
authors.initials: C
authors.lastname: Bock
mesh_terms: D002843:Chromatin; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D053263:Gene Regulatory Networks; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D000069550:Machine Learning; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin