Related Experiment Video

Updated: Dec 17, 2025

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
11:12

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Published on: August 1, 2018

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Super-enhancer acquisition drives oncogene expression in triple negative breast cancer

Ryan Raisner1, Russell Bainer2, Peter M Haverty3

  • 1Department of Discovery Oncology, Genentech, Inc., South San Francisco, California, United States of America.

Plos One
|June 26, 2020
PubMed

Insights

Researchers mapped active regulatory elements in Triple Negative Breast Cancer (TNBC) using ChIP-Seq. They discovered tumor-specific superenhancers and identified BAMBI as a potential therapeutic target for TNBC.

Area of Science:

  • Genomics and Epigenetics
  • Cancer Biology

Background:

  • Triple Negative Breast Cancer (TNBC) is an aggressive subtype with limited targeted treatment options.
  • Aberrant enhancer activity, beyond coding genome mutations, contributes to cancer development.
  • Understanding the regulatory landscape of TNBC is crucial for identifying new therapeutic strategies.

Purpose of the Study:

  • To map the active cis-regulatory landscape in TNBC using H3K27Ac ChIP-Seq.
  • To identify tumor-specific superenhancers and associated gene dependencies.
  • To uncover potential actionable therapeutic targets in TNBC.

Main Methods:

  • H3K27Ac chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to profile active enhancers.
  • Analysis of cis-regulatory elements to identify tumor-specific superenhancers.
  • CRISPR screening to identify gene dependencies associated with tumor-specific enhancers.

Main Results:

  • Distinct TNBC subtypes were associated with specific enhancer activity patterns.
  • Over 2,500 unique superenhancers were identified in tumor cells but not normal breast tissue.
  • CRISPR screening revealed tumor-specific dependencies, including a novel dependency on BAMBI.

Conclusions:

  • Active enhancer profiling reveals a complex regulatory landscape in TNBC.
  • Tumor-specific superenhancers highlight potential drivers of TNBC heterogeneity.
  • The TGFβ pseudo-receptor BAMBI is identified as a potential therapeutic vulnerability in TNBC.

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