DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features

Blood Cancer Discov. 8 May 2025 10.1158/2643-3230.BCD-24-0240

The genetic subtypes of Burkitt Lymphoma (BL) have been defined, whereas the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents, for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by EBV status or mutation status, leading to two epitypes, described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression and mutational differences between the epitypes support a model in which each arises from a distinct cell-of-origin. These results, pending validation in external cohorts, point to a refined risk assessment for BL patients who may experience inferior outcomes.

Supplemental Data

• GDC Manifests
  • CGCI-BLGSP Controlled-Access Data Download Manifest (4 Files)
  • CGCI-BLGSP Open-Access Data Download Manifest (8 Files)
  • CGCI-HTMCP-DLBCL Controlled-Access Data Download Manifest (2 Files)
  • CGCI-HTMCP-DLBCL Open-Access Data Download Manifest (4 Files)
• Clinical Data
  • Supplemental Clinical Data Update
• miRNA
  • CGCI-BLGSP miRNA-Seq Level 3 Data
  • CGCI-HTMCP-DLBCL miRNA-Seq Level 3 Data
• mRNA
  • CGCI-BLGSP mRNA-Seq Level 3 Data
  • CGCI-BLGSP mRNA-Seq Level 3 Data (Controlled)
  • CGCI-BLGSP mRNA-Seq Metadata
  • CGCI-HTMCP-DLBCL mRNA-Seq Level 3 Data
  • CGCI-HTMCP-DLBCL mRNA-Seq Level 3 Data (Controlled)
• Targeted Capture Sequencing
  • CGCI-BLGSP Targeted Capture Sequencing Level 3 Data (Controlled)
  • CGCI-BLGSP Targeted Capture Sequencing Design
  • CGCI-BLGSP Targeted Capture Sequencing Metadata
• Whole Genome Sequencing
  • CGCI-BLGSP WGS Level 2 Data
  • CGCI-BLGSP WGS Level 2 PromethION Data (Controlled)
  • CGCI-BLGSP WGS Level 3 Data (Controlled)
  • CGCI-BLGSP WGS Metadata
  • CGCI-HTMCP-DLBCL WGS Level 3 Data
  • CGCI-HTMCP-DLBCL WGS Level 3 Data (Controlled)
• Miscellaneous Files
  • CGCI-BLGSP Sample Matrix
  • CGCI-HTMCP-DLBCL Sample Matrix

Additional Resources

• Office of Cancer Genomics (link is external)

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