Analysis Tool Aids in Identifying Genes that Hijack Enhancers
You know that structural changes in genes are common in cancer, but how can you know which alterations actually drive disease? A new NCI-funded tool called “HAPI” (short for “Highly Active Promoter Interactions”) could help you gain insight into one possible outcome of these genetic changes.
In particular, using HAPI, you can spot structural changes linked to “hijacked” enhancers—DNA sequences that move from one location to another to boost overexpression of cancer-causing genes.
[callout]Read the full report, “3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression,” in Nature Communications. The HAPI analysis tool is publicly available.[/callout]
Corresponding author, Dr. Katherine Varley, of the University of Utah, said “HAPI not only helps you identify genes that many enhancers influence but also lets you see the location and contribution of those enhancers. This allows you to find HAPI genes that are interacting with enhancers hijacked from another genomic region, likely as a result of structural alterations.”
The authors note that you can use several tools to identify enhancer hijacking, but HAPI is unique because it allows you to prioritize the gene targets and underlying functional enhancers.
Co-corresponding author, Dr. Xiaoyang Zhang, also from the University of Utah, said, “Prioritizing is essential because most of the structural variants are passenger events. They’re passed along but ultimately don’t impact function. With our approach, you can prioritize the ones that are more likely to affect expression of cancer-causing genes.”
This tool could help uncover new therapeutic strategies. As noted by Dr. Zhang, “If we can better understand enhancer hijacking events, we can find new ways to silence oncogenes. By linking hijacked enhancers to structural changes in tumor genomes, we also could identify cancer-specific targets for therapeutics (such as ZNF, TALEN and CRISPR).”