Hassler, MR; Pulverer, W; Lakshminarasimhan, R; Redl, E; Hacker, J; Garland, GD; Merkel, O; Schiefer, AI; Simonitsch-Klupp, I; Kenner, L; Weisenberger, DJ; Weinhaeusel, A; Turner, SD; Egger, G
Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.
Cell Rep. 2016; 17(2):596-608
Autor/innen der Vetmeduni Vienna:
Institut für Pathologie, Abteilung für Labortierpathologie
- Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+) and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy.Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Cell Line, Tumor
Lymphoma, Large-Cell, Anaplasticgeneticspathology