期刊
CELL REPORTS
卷 17, 期 2, 页码 596-608出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.09.018
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类别
资金
- Austrian Science Foundation (FWF) [P 27616, V 102]
- L'Oreal for Women in Science grant
- Bloodwise
- FWF [P 26011, P 29251]
- MSCA-ITN-ETN ALKATRAS [675712]
- Zymo Research Corporation
- Austrian Science Fund (FWF) [P27616] Funding Source: Austrian Science Fund (FWF)
- Biotechnology and Biological Sciences Research Council [989632] Funding Source: researchfish
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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