Ryan, Drier et al. link enhancers to oncogene activation in B cell lymphoma

Russell Ryan and Yotam Drier describe PEAR-ChIP, a novel approach for the detection of genomic rearrangements associated with acetylated chromatin. The authors apply this technology to patient samples from several distinct subtypes of B cell lymphoma, revealing therapeutically targetable rearrangements, and uncovering novel mechanisms by which the oncogenes MYC and BCL6 are regulated via native and rearranged enhancers.

Key findings:

  • PEAR-ChIP allows for genome-wide enhancer activity and rearrangement detection in a single protocol
  • PEAR-ChIP analysis of mantle cell lymphoma, diffuse large B cell lymphoma, and chronic lymphocytic leukemia reveals “enhancer hijacking”, enhancer amplification, gene fusion, and inactivating rearrangements affecting numerous cancer genes, including CCND1, BCL2, MYC, BCL6, PDCD1LG2, CIITA, and others.
  • Lymphoma subtype-specific MYC enhancers are active in lymphomas lacking MYC rearrangements, and are associated with SNPs linked to inherited lymphoma risk.
  • Germinal center-specific BCL6 enhancers are activated by the oncogenic transcription factor MEF2B, and can activate MYC via enhancer hijacking in a “pseudo-double-hit” t(3;8)(q27;q24) rearrangement.


Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma.

Ryan RJ, Drier Y, Whitton H, Cotton MJ, Kaur J, Issner R, Gillespie S, Epstein CB, Nardi V, Sohani AR, Hochberg EP, Bernstein BE. Cancer Discov. 2015 Jul 30. pii: CD-15-0370.