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Title
Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling
AuthorEgger, Gerda ; Turner, Suzanne D. ; Weinhaeusel, Andreas ; Weisenberger, Daniel J. ; Kenner, Lukas ; Simonitsch-Klupp, Ingrid ; Schiefer, Ana-Iris ; Merkel, Olaf ; Garland, Gavin D. ; Hacker, Julia ; Redl, Elisa ; Lakshminarasimhan, Ranjani ; Pulverer, Walter ; Hassler, Melanie R.
Published in
Cell Reports, Cambridge, 2016, Vol. 17, Issue 2, page 596-608
PublishedCambridge : Cell Press, 2016
LanguageEnglish
Document typeJournal Article
Keywords (EN)tumor-suppressor genes / non-hodgkins-lymphoma / npm-alk / signaling pathways / fusion protein / kinase / expression / cancer / transcription / disease
Project-/ReportnumberP 27616-B20
ISSN2211-1247
URNurn:nbn:at:at-ubmuw:3-1619 Persistent Identifier (URN)
DOI10.1016/j.celrep.2016.09.018 
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 The work is publicly available
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Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling [11.84 mb]
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Abstract (English)

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.

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CC-BY-License (4.0)Creative Commons Attribution 4.0 International License