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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
BRD7 promoter hypermethylation as an indicator of well differentiated oral squamous cell carcinomas
Anandh Balasubramanian1, Ramkumar Subramaniam, Vivek Narayanan
1Oral and Maxillofacial Surgery, Faculty of Dentistry, Sri Ramachandra University, Potheri, India
Background:
Promoter hypermethylation mediated gene silencing of tumor suppressor genes is considered as most frequent mechanism than genetic aberrations such as mutations in the development of cancers. BRD7 is a single bromodomain containing protein that functions as a subunit of SWI/SNF chromatin-remodeling complex to regulate transcription. It also interacts with the well know tumor suppressor protein p53 to trans- activate genes involved in cell cycle arrest. Loss of expression of BRD7 has been observed in breast cancers and nasopharyngeal carcinomas due to promoter hypermethylation. However, the genetic status of BRD7 in oral squamous cell carcinomas (OSCCs) is not known, although OSCC is one of the most common among all reported cancers in the Indian population. Hence, in the present study we investigated OSCC samples to determine the occurrence of hypermethylation in the promoter region of BRD7 and understand its prevalence.
Materials And Methods:
Genomic DNA extracted from biopsy tissues of twenty three oral squamous cell carcinomas were digested with methylation sensitive HpaII type2 restriction enzyme that recognizes and cuts unmethylated CCGG motifs. The digested DNA samples were amplified with primers flanking the CCGG motifs in promoter region of BRD7 gene. The PCR amplified products were analyzed by agarose gel electrophoresis along with undigested amplification control.
Results:
Methylation sensitive enzyme technique identified methylation of BRD7 promoter region seventeen out of twenty three (74%) well differentiated oral squamous cell carcinoma samples.
Conclusions:
The identification of BRD7 promoter hypermethylation in 74% of well differentiated oral squamous cell carcinomas indicates that the methylation dependent silencing of BRD7 gene is a frequent event in carcinogenesis. To the best of our knowledge, the present study is the first to report the occurrence of BRD7and its high prevalence in oral squamous cell carcinomas.
Insights
Promoter hypermethylation frequently silences the BRD7 tumor suppressor gene in oral squamous cell carcinomas (OSCCs). This study found BRD7 promoter hypermethylation in 74% of OSCC samples, indicating its role in oral cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Promoter hypermethylation is a frequent mechanism of tumor suppressor gene silencing in cancer.
- BRD7, a component of the SWI/SNF chromatin-remodeling complex, acts as a tumor suppressor and its loss of expression is observed in various cancers.
- The epigenetic status of BRD7 in oral squamous cell carcinomas (OSCCs) was previously unknown.
Purpose of the Study:
- To investigate the occurrence and prevalence of BRD7 promoter hypermethylation in oral squamous cell carcinoma (OSCC) samples.
- To determine if BRD7 promoter hypermethylation is a frequent event in the development of OSCC.
Main Methods:
- Genomic DNA was extracted from 23 OSCC biopsy tissues.
- DNA was digested using the methylation-sensitive restriction enzyme HpaII.
- The promoter region of the BRD7 gene was amplified using PCR, and products were analyzed via agarose gel electrophoresis.
Main Results:
- Methylation-sensitive enzyme analysis revealed BRD7 promoter hypermethylation in 17 out of 23 (74%) well-differentiated OSCC samples.
- The findings indicate a high prevalence of BRD7 promoter hypermethylation in OSCC.
Conclusions:
- BRD7 promoter hypermethylation is a frequent epigenetic event in oral squamous cell carcinoma (OSCC) carcinogenesis.
- The study is the first to report the occurrence and high prevalence of BRD7 promoter hypermethylation in OSCC.

