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Updated: Apr 12, 2026
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Regulators associated with clinical outcomes revealed by DNA methylation data in breast cancer
Matthew H Ung1, Frederick S Varn1, Shaoke Lou1
1Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Abstract:
The regulatory architecture of breast cancer is extraordinarily complex and gene misregulation can occur at many levels, with transcriptional malfunction being a major cause. This dysfunctional process typically involves additional regulatory modulators including DNA methylation. Thus, the interplay between transcription factor (TF) binding and DNA methylation are two components of a cancer regulatory interactome presumed to display correlated signals. As proof of concept, we performed a systematic motif-based in silico analysis to infer all potential TFs that are involved in breast cancer prognosis through an association with DNA methylation changes. Using breast cancer DNA methylation and clinical data derived from The Cancer Genome Atlas (TCGA), we carried out a systematic inference of TFs whose misregulation underlie different clinical subtypes of breast cancer. Our analysis identified TFs known to be associated with clinical outcomes of p53 and ER (estrogen receptor) subtypes of breast cancer, while also predicting new TFs that may also be involved. Furthermore, our results suggest that misregulation in breast cancer can be caused by the binding of alternative factors to the binding sites of TFs whose activity has been ablated. Overall, this study provides a comprehensive analysis that links DNA methylation to TF binding to patient prognosis.
Insights
This study reveals how DNA methylation and transcription factor (TF) binding interplay in breast cancer. We identified key TFs influencing prognosis, offering new insights into cancer regulatory networks.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Breast cancer's complexity involves gene misregulation, often at the transcriptional level.
- DNA methylation is a key modulator in this dysfunctional transcriptional process.
- The interaction between transcription factor (TF) binding and DNA methylation is crucial in cancer regulation.
Purpose of the Study:
- To systematically identify potential TFs involved in breast cancer prognosis via their association with DNA methylation changes.
- To infer TFs misregulated in different breast cancer clinical subtypes using TCGA data.
- To explore the relationship between DNA methylation, TF binding, and patient outcomes.
Main Methods:
- Systematic motif-based in silico analysis of breast cancer DNA methylation and clinical data.
- Utilizing The Cancer Genome Atlas (TCGA) dataset for comprehensive analysis.
- Inferring TF involvement through association with DNA methylation patterns.
Main Results:
- Identified known TFs linked to p53 and estrogen receptor (ER) subtypes of breast cancer.
- Predicted novel TFs potentially involved in breast cancer prognosis.
- Provided evidence that alternative factor binding can occur at ablated TF sites, contributing to misregulation.
Conclusions:
- Established a comprehensive link between DNA methylation, TF binding, and breast cancer patient prognosis.
- Highlighted the complex regulatory interactome in breast cancer.
- Offered potential new targets for understanding and treating breast cancer subtypes.
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