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Cell Rep. 2016 Oct 4;17(2):596-608. doi: 10.1016/j.celrep.2016.09.018.

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

Author information

1
Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria.
2
Health & Environment Department, Molecular Diagnostics, Austrian Institute of Technology (AIT), 1190 Vienna, Austria.
3
Department of Urology, Norris Comprehensive Cancer Center, University of Southern California-Los Angeles, Los Angeles, CA 90089, USA.
4
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK.
5
Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria; European Research Initiative on ALK-Related Malignancies (ERIA), Cambridge CB2 0QQ, UK.
6
Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, 1090 Vienna, Austria; Unit of Pathology of Laboratory Animals (UPLA), University of Veterinary Medicine Vienna, 1210 Vienna, Austria; European Research Initiative on ALK-Related Malignancies (ERIA), Cambridge CB2 0QQ, UK.
7
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California-Los Angeles, Los Angeles, CA 90089, USA.
8
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK; European Research Initiative on ALK-Related Malignancies (ERIA), Cambridge CB2 0QQ, UK.
9
Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria; European Research Initiative on ALK-Related Malignancies (ERIA), Cambridge CB2 0QQ, UK. Electronic address: gerda.egger@meduniwien.ac.at.

Abstract

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.

KEYWORDS:

DNA methylation; NPM-ALK; anaplastic large-cell lymphoma

PMID:
27705804
PMCID:
PMC6066089
DOI:
10.1016/j.celrep.2016.09.018
[Indexed for MEDLINE]
Free PMC Article

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