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Type of publication: Journal Article
Type of document: Full Paper

Year: 2016

Authors: 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

Title: Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.

Source: Cell Rep. 2016; 17(2):596-608

Authors Vetmeduni Vienna:

Kenner Lukas

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals

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.

Keywords Pubmed: Adolescent
Cell Differentiationgenetics
Cell Line, Tumor
DNA Methylationgenetics
Genome, Humangenetics
Lymphocyte Activationgenetics
Lymphoma, Large-Cell, Anaplasticgeneticspathology
Middle Aged
Protein-Tyrosine Kinasesgenetics
Signal Transduction
Young Adult

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