Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.
Cell Rep
; 17(2): 596-608, 2016 10 04.
Article
en En
| MEDLINE
| ID: mdl-27705804
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Genoma Humano
/
Linfoma Anaplásico de Células Grandes
/
Metilación de ADN
Tipo de estudio:
Etiology_studies
Límite:
Adolescent
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Adult
/
Aged
/
Child
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Cell Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Austria