Zeitschriftenaufsatz
|
2016
Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling
Autor:in
Hassler, Melanie R.; Pulverer, W.; Lakshminarasimhan, Ranjani; Redl, Elisa; Hacker, J. L.; Garland, Gavin; Merkel, Olaf; Schiefer, Ana-Iris; Simonitsch-Klupp, Ingrid; Kenner, Lukas; Weisenberger, Daniel; Weinhaeusel, Andreas; Turner, Suzanne; Egger, Gerda
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
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.
Schlagwörter
Adolescent; Adult; Aged; Cell Differentiationgenetics; Cell Line, Tumor; Child; DNA Methylationgenetics; Female; Genome, Humangenetics; Humans; Lymphocyte Activationgenetics; Lymphoma, Large-Cell, Anaplasticgeneticspathology; Male; Middle Aged; Protein-Tyrosine Kinasesgenetics; Signal Transduction; Young Adult
Dokumententyp
Originalarbeit
CC Lizenz
CCBY
Open Access Type
Gold
ISSN/eISSN
2211-1247 -
10.1016/j.celrep.2016.09.018
WoS ID
PubMed ID