Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks

André F. Rendeiro, Christian Schmidl, Jonathan C. Strefford, Renata Walewska, Zadie Davis, Matthias Farlik, David Oscier and Christoph Bock ()
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André F. Rendeiro: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Christian Schmidl: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Jonathan C. Strefford: Faculty of Medicine, Cancer Sciences, University of Southampton
Renata Walewska: Royal Bournemouth Hospital
Zadie Davis: Royal Bournemouth Hospital
Matthias Farlik: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
David Oscier: Royal Bournemouth Hospital
Christoph Bock: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11938

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