Related Experiment Video

Updated: Jul 8, 2025

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
13:19

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer

Published on: November 2, 2013

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HYENA detects oncogenes activated by distal enhancers in cancer

Anqi Yu1, Ali E Yesilkanal1, Ashish Thakur2

  • 1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA.

Biorxiv : the Preprint Server for Biology
|December 11, 2023
PubMed

Insights

Structural variations in cancer genomes can activate oncogenes. Our study identifies novel oncogenes, including non-coding genes, driven by enhancer hijacking, revealing new cancer mechanisms.

Area of Science:

  • Genomics
  • Cancer Biology
  • Bioinformatics

Background:

  • Somatic structural variations (SVs) can alter genome organization and gene expression in cancer.
  • Enhancer hijacking, a mechanism where SVs relocate enhancers to activate proto-oncogenes, has primarily focused on protein-coding genes.
  • Understanding SV-driven oncogene activation is crucial for cancer research.

Approach:

  • Developed HYENA, a computational algorithm to identify candidate oncogenes (protein-coding and non-coding) activated by enhancer hijacking.
  • Utilized tumor whole-genome and transcriptome sequencing data from 1,146 tumors across 25 adult cancer types.
  • Employed a rank-based regression model to link elevated gene expression with somatic SVs.

Key Points:

  • Identified 108 candidate oncogenes, including numerous non-coding genes, activated by enhancer hijacking.
  • Discovered that the long non-coding RNA TOB1-AS1 is activated by SVs in 10% of pancreatic cancers via altered 3D genome structure.
  • Demonstrated that high TOB1-AS1 expression promotes cell invasion and metastasis.

Conclusions:

  • HYENA expands the scope of enhancer hijacking studies to include non-coding genes.
  • Genetic alterations in non-coding regions significantly contribute to tumorigenesis and cancer progression.
  • This work provides new insights into the role of SVs and non-coding elements in cancer development.

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