Abstract
9558 Background: The mitotic checkpoint is a failsafe mechanism for the cell to ensure accurate chromosome segregation during mitosis. Mutations in genes encoding essential checkpoint proteins lead to chromosome instability and promote carcinogenesis. The BUB3 and BUBR1 genes are essential components of the mitotic checkpoint pathway. AIM: To determine the role of aberrant promoter methylation of the genes BUB3 and BUBR1 in lung cancer. Materials and Methods: We performed Restriction Landmark Genomic Scanning (RLGS) in 20 Non-Small Cell Lung Cancer (NSCLC) samples and found the mitotic checkpoint gene BUR1 to be methylated. We then decided to look for methylation in other members of the BUB family. DNA was isolated from 53 microdissected freshly frozen NSCLC samples. Bisulphite treated DNA was then subjected to MSP following standard techniques. Results: BUR1 was found to be methylated in 47% (25/53) samples and BUB3 to be methylated in 45% (24/53) samples. It was surprising for us to find that the combination of both genes is methylated in 77% of the lung cancer samples analyzed. Conclusions: methylated of the mitotic checkpoint genes BUB3 and BUBR1 is a common epigenetic event in lung cancer. No significant financial relationships to disclose.
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