BRD7 Promoter Hypermethylation as an Indicator of Well Differentiated Oral Squamous Cell Carcinomas

Background: Promoter hypermethylation mediated gene silencing of tumor suppressor genes is consideredas most frequent mechanism than genetic aberrations such as mutations in the development of cancers. BRD7is a single bromodomain containing protein that functions as a subunit of SWI/SNF chromatin-remodelingcomplex to regulate transcription. It also interacts with the well know tumor suppressor protein p53 to transactivategenes involved in cell cycle arrest. Loss of expression of BRD7 has been observed in breast cancers andnasopharyngeal carcinomas due to promoter hypermethylation. However, the genetic status of BRD7 in oralsquamous cell carcinomas (OSCCs) is not known, although OSCC is one of the most common among all reportedcancers in the Indian population. Hence, in the present study we investigated OSCC samples to determine theoccurrence 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 weredigested with methylation sensitive HpaII type2 restriction enzyme that recognizes and cuts unmethylatedCCGG motifs. The digested DNA samples were amplified with primers flanking the CCGG motifs in promoterregion of BRD7 gene. The PCR amplified products were analyzed by agarose gel electrophoresis along withundigested amplification control.
Results: Methylation sensitive enzyme technique identified methylation ofBRD7 promoter region seventeen out of twenty three (74%) well differentiated oral squamous cell carcinomasamples.
Conclusions: The identification of BRD7 promoter hypermethylation in 74% of well differentiatedoral squamous cell carcinomas indicates that the methylation dependent silencing of BRD7 gene is a frequentevent in carcinogenesis. To the best of our knowledge, the present study is the first to report the occurrence ofBRD7and its high prevalence in oral squamous cell carcinomas.