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2016 ; 7
(ä): 11938
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Chromatin accessibility maps of chronic lymphocytic leukaemia identify
subtype-specific epigenome signatures and transcription regulatory networks
#MMPMID27346425
Rendeiro AF
; Schmidl C
; Strefford JC
; Walewska R
; Davis Z
; Farlik M
; Oscier D
; Bock C
Nat Commun
2016[Jun]; 7
(ä): 11938
PMID27346425
show ga
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.