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Updated: Aug 8, 2026
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas
Igor Girault1, Sengül Tozlu, Rosette Lidereau
1Laboratoire d'Oncogénétique-Institut National de la Santé et de la Recherche Médicale E0017 Centre René Huguenin, F-92211 St-Cloud, France.
Purpose:
Three genes, namely DNA methyltransferase (DNMT) 1, DNMT3A, and DNMT3B, coding for DNMTs that affect promoter methylation status are thought to play an important role in the development of cancers. Little is known of the biological and clinical significance of these genes in human breast cancer.
Experimental Design:
We used real-time reverse transcription-PCR assays to quantify the mRNA expression of the three DNMT genes in a series of 130 breast cancer patients. We also sought relationships between mRNA levels of the DNMTs and those of 20 target genes involved in the DNMT pathway (subgroup of 46 breast tumors).
Results:
The DNMT3B gene showed the highest range of expression (81.8 compared with 16.6 and 14 for DNMT1 and DNMT3A, respectively). DNMT3B was overexpressed in 30% of the patients (5.4 and 3.1% for DNMT1 and DNMT3A, respectively). DNMT3B overexpression was significantly related to Scarff, Bloom, and Richardson histopathological grade III (P = 0.002), ERalpha negativity (P = 0.0015), and strong MKI67 expression (P = 3 x 10(-6)). In univariate analysis, DNMT3B overexpression was associated with poor relapse-free survival in the subgroup of patients who received adjuvant hormone therapy (with or without chemotherapy; P = 0.0064). Although the poor prognosis associated with DNMT3B overexpression was confirmed by univariate analysis in an independent series of 98 postmenopausal women exclusively treated with adjuvant tamoxifen therapy (P = 0.0036), DNMT3B expression status did not persist as an independent prognostic factor in multivariate analysis.
Conclusions:
Although we failed to identify underexpression of specific target genes associated with DNMT increasing expression, the frequent overexpression of DNMT3B in this breast tumor series points to DNMT3B as a potential new therapeutic target in breast cancer.
Insights
DNA methyltransferase 3B (DNMT3B) is frequently overexpressed in breast cancer, correlating with aggressive tumor features. While not an independent prognostic factor, DNMT3B overexpression suggests it may be a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- DNA methyltransferases (DNMTs) regulate promoter methylation and are implicated in cancer development.
- The roles of DNMT1, DNMT3A, and DNMT3B in human breast cancer remain largely uncharacterized.
Purpose of the Study:
- To investigate the biological and clinical significance of DNMT1, DNMT3A, and DNMT3B in human breast cancer.
- To quantify mRNA expression levels of these DNMT genes in breast tumors.
- To explore relationships between DNMT expression and clinicopathological features or target genes.
Main Methods:
- Real-time reverse transcription-PCR was used to quantify mRNA expression of DNMT1, DNMT3A, and DNMT3B in 130 breast cancer patients.
- Associations between DNMT mRNA levels and clinicopathological parameters were analyzed.
- Relationships with 20 target genes in the DNMT pathway were examined in a subset of 46 tumors.
Main Results:
- DNMT3B exhibited the widest expression range and was overexpressed in 30% of breast cancer patients.
- DNMT3B overexpression significantly correlated with high histopathological grade, ERalpha negativity, and strong MKI67 expression.
- Univariate analysis indicated DNMT3B overexpression was associated with poor relapse-free survival in patients receiving adjuvant hormone therapy or tamoxifen.
Conclusions:
- Frequent DNMT3B overexpression in breast tumors suggests its potential as a novel therapeutic target.
- Further research is needed to elucidate the precise role and clinical utility of DNMT3B in breast cancer treatment.
