Key Role of Promoter Methylation and Inactivation of MCPH1 Gene in Brain Tumors

Abstract

Background: Microcephalin (MCPH1/BIRT1) is a putative tumor suppressor gene which has recently seized great attentions in cancer studies. The present study was conducted to seek the impact of MCPH1 promoter methylation on development of brain tumors and telomere repeat length (TRL). Methods: The brain tissue section provided from brain tumor patients and two normal brain autopsies were undergone DNA isolation. DNA samples treated with bisulfite sodium using DNA modification kit (Qiagen) were amplified in methylation specific polymerization chain reaction (MSP-PCR) confirmed by sequencing. Protein expression analysis was performed by immunofluorescence (IF) assay using antibodies against MCPH1, cyclin E and CDC25A proteins. The TRL of brain tumor patients was determined through quantitative fluorescent in situ hybridization (Q-FISH). Results: The MCPH1 gene promoter was methylated in 96.6% of the patients consistent with protein expression pattern and the telomere statue was confirmed by low or absence of signal in tumor cells. Conclusion: MCPH1 promoter methylation had strong association with TRL, tumor’s grade and stage (P < 0.05). TRL was meaningfully associated with grade and subtype pathology of brain tumors (P = 0.01). Further studies are required to clarify the exact role of MCPH1 gene on TRL and tumor suppression especially in brain tumors. J Neurol Res. 2014;4(5-6):133-138 doi: http://dx.doi.org/10.14740/jnr295e