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Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Array-based multiplex analysis of DNA methylation in breast cancer tissues
Anatoliy A Melnikov1, Denise M Scholtens, Elizabeth L Wiley
1Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago Illinois, USA.
The Journal of Molecular Diagnostics : JMD
|January 1, 2008
Summary
Developing a multigene DNA methylation signature improves cancer detection accuracy in breast tissue. This approach identifies specific methylation patterns for early diagnosis, paving the way for a novel diagnostic assay.
Area of Science:
- Oncology
- Genetics
- Biomarker Discovery
Background:
- Abnormal DNA methylation is a hallmark of cancer, yet a reliable methylation-based diagnostic test is lacking.
- Analyzing single genes in heterogeneous clinical samples limits cancer detection accuracy.
Purpose of the Study:
- To develop a multigene methylation signature for improved cancer detection.
- To evaluate the potential of selecting informative genes for a diagnostic assay using breast cancer tissues.
Main Methods:
- A microarray-based technique analyzed methylation of 56 promoters in 138 breast cancer tissue specimens.
- Fisher's exact test identified informative promoters, and the naïve Bayes algorithm designed a composite biomarker.
Main Results:
- Specific methylation signatures were identified for atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma.
- The developed biomarker achieved 72.4% sensitivity and 74.7% specificity for ductal carcinoma in situ and invasive ductal carcinoma.
- High accuracy was observed for atypical ductal hyperplasia detection (87.5% sensitivity, 95% specificity).
Conclusions:
- Informative cancer-specific methylation signatures can be detected in heterogeneous tissue specimens.
- These findings support the development of a novel, multigene methylation-based diagnostic assay for breast cancer.
