Insights into molecular characteristics of anaplastic large cell lymphoma by genome-wide DNA methylation profiling

Aberrant DNA methylation patterns of malignant cells allow for the study of the tumor phenotype and behavior, and can be used for tumor classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK positive and negative anaplastic large cell lymphoma (ALCL). Differences in DNA methylation of tumor cells compared to normal T cells concern pathways that are implicated in T cell development and function and reveal a close relationship to distinct developmental stages of thymocytes. We find DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs, such as AP1. Our results suggest a direct relationship of oncogenic signaling with epigenetic modifications via transcription factor induction and occupancy. DNA from 15 samples (5 Alk- tumor; 5 Alk+ tumors; 5 CD3 cells) were subjected to genome wide methylation analysis using Illuminas Infinium HumanMethylation450 BeadChip. Findings of the BeadChip analysis have been validated using MSP, COBRA and ChiP analysis.