Analysis of retrotransposon subfamily DNA methylation reveals novel early epigenetic changes in chronic lymphocytic leukaemia.

Analysis of retrotransposon subfamily DNA methylation reveals novel early epigenetic changes in chronic lymphocytic leukaemia. Haematologica. 2020 Jan 09;: Authors: Barrow TM, Wong Doo N, Milne RL, Giles GG, Willmore E, Strathdee G, Byun HM Abstract Retrotransposons such as LINE-1 and Alu comprise >25% of the human genome. While global hypomethylation of these elements has been widely reported in solid tumours, their epigenetic dysregulation is yet to be characterised in chronic lymphocytic leukaemia, and there has been scant consideration of their evolutionary history that mediates sensitivity to hypomethylation. Here, we developed an approach for locus- and evolutionary subfamily-specific analysis of retrotransposons using the Illumina Infinium Human Methylation 450K microarray platform, which we applied to publicly-available datasets from chronic lymphocytic leukaemia and other haematological malignancies. We identified 9,797 microarray probes mapping to 117 LINE-1 subfamilies and 13,130 mapping to 37 Alu subfamilies. Of these, 10,782 were differentially methylated (PFDR<0.05) in chronic lymphocytic leukaemia patients (n=139) compared with healthy individuals (n=14), with enrichment at enhancers (p=0.002). Differential methylation was associated with evolutionary age of LINE-1 (r2=0.31, p=0.003) and Alu (r2=0.74, p=0.002) elements, with greater hypomethylation of older subfamilies (L1M, AluJ). Locus-specific hypomethylation ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research