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.
- 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.
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.