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Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
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A DNA Methylation-Based Gene Signature Can Predict Triple-Negative Breast Cancer Diagnosis.
Saioa Mendaza1, David Guerrero-Setas1,2, Iñaki Monreal-Santesteban1
1Molecular Pathology of Cancer Group, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, 31008 Pamplona, Spain.
Biomedicines
|October 23, 2021
Summary
We identified a novel DNA methylation signature for diagnosing triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype. This signature shows high accuracy in distinguishing TNBC from normal tissues, even in early stages.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
- Current TNBC diagnosis relies on immunohistochemistry, which has interlaboratory variability.
- DNA methylation aberrations are prevalent in breast cancer, suggesting potential for diagnostic biomarkers.
Purpose of the Study:
- To identify novel DNA methylation biomarkers for accurate TNBC diagnosis.
- To develop a robust methylation signature for TNBC classification.
- To validate the diagnostic potential of methylation markers in clinical samples and plasma.
Main Methods:
- Generated a differentially methylated probe signature for TNBC classification using tissue samples.
- Validated the signature's robustness in larger independent cohorts from the Gene Expression Omnibus (GEO) repository.
- Confirmed hypomethylation of specific probes (FLJ43663, PBX1, RASA3) in TNBC tissues via pyrosequencing.
- Assessed methylation levels of FLJ43663 in cell-free DNA from TNBC patient plasma.
Main Results:
- A DNA methylation signature was generated with a low error rate (0.083) in initial tissue samples.
- The signature demonstrated high robustness and accuracy (error rate = 0.006) in larger GEO cohorts.
- Hypomethylation of FLJ43663, PBX1, and RASA3 was validated in early-stage TNBC tissues.
- Significantly lower FLJ43663 methylation was observed in plasma cell-free DNA of TNBC patients compared to healthy donors.
Conclusions:
- A novel DNA methylation signature shows significant potential for accurate TNBC diagnosis.
- The identified methylation markers, including FLJ43663, PBX1, and RASA3, are promising for early TNBC detection.
- Plasma-based methylation analysis of FLJ43663 could offer a non-invasive diagnostic approach for TNBC.
