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Updated: Aug 28, 2025

Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
CDH1 (E-cadherin) Gene Methylation in Human Breast Cancer: Critical Appraisal of a Long and Twisted Story
1Institute of Pathology, Medical School Hannover, D-30623 Hannover, Germany.
Abstract:
Epigenetic inactivation of a tumor suppressor gene by aberrant DNA methylation is a well-established defect in human tumor cells, complementing genetic inactivation by mutation (germline or somatic). In human breast cancer, aberrant gene methylation has diagnostic, prognostic, and predictive potential. A prominent example is the hypermethylation of the CDH1 gene, encoding the adhesion protein E-Cadherin ("epithelial cadherin"). In numerous publications, it is reported as frequently affected by gene methylation in human breast cancer. However, over more than two decades of research, contradictory results concerning CDH1 gene methylation in human breast cancer accumulated. Therefore, we review the available evidence for and against the role of DNA methylation of the CDH1 gene in human breast cancer and discuss in detail the methodological reasons for conflicting results, which are of general importance for the analysis of aberrant DNA methylation in human cancer specimens. Since the loss of E-cadherin protein expression is a hallmark of invasive lobular breast cancer (ILBC), special attention is paid to CDH1 gene methylation as a potential mechanism for loss of expression in this special subtype of human breast cancer. Proper understanding of the methodological basis is of utmost importance for the correct interpretation of results supposed to demonstrate the presence and clinical relevance of aberrant DNA methylation in cancer specimens.
Insights
Aberrant DNA methylation of the CDH1 gene is investigated in human breast cancer. This review examines conflicting evidence and methodological issues, particularly for invasive lobular breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Aberrant DNA methylation of tumor suppressor genes is a hallmark of human cancers.
- The CDH1 gene, encoding E-cadherin, is frequently implicated in breast cancer methylation.
- Conflicting reports exist regarding CDH1 gene methylation in human breast cancer.
Purpose of the Study:
- To review evidence for and against CDH1 gene methylation in human breast cancer.
- To discuss methodological reasons for conflicting results in DNA methylation analysis.
- To investigate CDH1 methylation as a cause of E-cadherin loss in invasive lobular breast cancer.
Main Methods:
- Systematic review of published literature on CDH1 gene methylation in breast cancer.
- Analysis of methodological variations in DNA methylation detection assays.
- Correlation of CDH1 methylation status with E-cadherin protein expression, especially in invasive lobular breast cancer.
Main Results:
- Evidence supporting and refuting CDH1 gene hypermethylation in breast cancer was identified.
- Methodological differences in sample handling, DNA extraction, and methylation detection methods contribute to discrepancies.
- CDH1 methylation is a potential mechanism for E-cadherin loss in invasive lobular breast cancer, though not consistently observed.
Conclusions:
- The role of CDH1 gene methylation in human breast cancer remains controversial due to inconsistent findings.
- Standardization of methodologies is crucial for accurate assessment of aberrant DNA methylation in cancer research.
- Understanding CDH1 methylation's role is vital for the diagnosis and treatment of invasive lobular breast cancer.
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