Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

Cancer Cell. 2016 Nov 14;30(5):806-821. doi: 10.1016/j.ccell.2016.09.014.

Abstract

We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

Keywords: ChIP-seq; DNA looping; DNA methylation; SOX11; chromatin; enhancer; epigenomics; lymphoma; mantle cell lymphoma; whole-genome bisulfite sequencing.

Publication types

  • Comment

MeSH terms

  • B-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cell Lineage
  • Computer Simulation
  • DNA Methylation*
  • Enhancer Elements, Genetic*
  • Epigenesis, Genetic
  • Epigenomics / methods*
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lymphoma, Mantle-Cell / genetics*
  • SOXC Transcription Factors / genetics

Substances

  • SOX11 protein, human
  • SOXC Transcription Factors