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Updated: May 18, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma
Kavita M Pattani1, Ethan Soudry, Chad A Glazer
1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Purpose:
Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented.
Experimental Design:
In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC) tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene.
Results:
From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines.
Conclusion:
In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.
Insights
Proto-oncogene activation via promoter demethylation is rare. This study identified MAGEB2 as demethylated and overexpressed in head and neck cancer, promoting cell growth.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Promoter hypermethylation typically silences tumor suppressor genes.
- Proto-oncogene activation by promoter demethylation is less understood in cancer.
Purpose of the Study:
- To discover epigenetically activated proto-oncogenes in head and neck squamous cell carcinoma (HNSCC) using whole-genome analysis.
- To investigate the role of promoter demethylation in HNSCC pathogenesis.
Main Methods:
- Whole-genome analysis of HNSCC tissues and normal mucosa.
- Affymetrix expression microarray and bisulfite sequencing.
- Quantitative methylation-specific PCR (QMSP) and RT-PCR for candidate gene validation.
- Functional studies on MAGEB2 in oral keratinocyte cell lines.
Main Results:
- Identified MAGEB2 with significant promoter demethylation in HNSCC tissues.
- Found significantly higher MAGEB2 expression in HNSCC tumors compared to normal tissues.
- MAGEB2 demonstrated growth-promoting effects in minimally transformed oral keratinocytes.
Conclusions:
- MAGEB2 is activated by promoter demethylation in HNSCC.
- MAGEB2 exhibits growth-promoting activity in early-stage oral cells.
- Further research is required to elucidate MAGEB2's precise role in HNSCC progression.
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