Role of Concurrent Methylation Pattern of MGMT, TP53 and CDKN2A Genes in the Prognosis of High Grade Glioma
- *Corresponding Author:
- Chetan GK
Department of Human Genetics
National Institute of Mental Health and Neurosciences (NIMHANS)
E-mail: [email protected]
Received date: December 27, 2015 Accepted date: January 22, 2016 Published date: January 25, 2016
Citation: Chetan GK, Jeru-Manoj Manuel, Ghosh D, Sibin MK, Venkatesh HN, et al. (2016) Role of Concurrent Methylation Pattern of MGMT, TP53 and CDKN2A Genes in the Prognosis of High Grade Glioma. J Carcinog Mutagene 7:250. doi: 10.4172/2157-2518.1000250
Copyright: © 2016 Chetan GK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: High grade glioma (HGG) patients show poor prognosis and survival. Promoter methylation of MGMT gene induces altered methylation profile across cell cycle regulating genes. Correlating the promoter methylation status between important tumor suppressor genes could enhance the current understanding of glioma progression.
Methods: We analysed individual and concurrent methylation statuses’ of three tumor suppressor genes, MGMT, TP53 and CDKN2A in different types of HGG and their probable effect on progression free survival. MS-PCR was used to analyse the methylation statuses from 48 HGG tumor samples.
Results: Promoter methylation was observed in 89.5% (43/48) of our cohort in atleast one of the genes, most frequent in MGMT (75%), followed by CDKN2A (35.4%) and TP53 (29.2%). MGMT methylation and TP53 unmethylation individually were significant (p=0.001 and 0.016) for PFS at 14 months. MGMT methylation with therapy (RT/CT+RT) was seen to improve PFS. Concurrent methylation was notably seen in oligodendroglial tumors, the frequency between MGMT: TP53 was 20.83%, MGMT: CDKN2A (27.1%) and TP53:CDKN2A (14.6%). Interestingly, concurrent methylation of MGMT: TP53:CDKN2A (12.5%) had better 14 month-PFS proportion (80%).
Conclusion: Two gene concurrent methylation of MGMT along with either TP53 or CDKN2A decreased the PFS rate, indicating the negative effect of methylation of TP53 or CDKN2A. However, concurrent methylation of all three genes had better prognosis, but could be mainly due to influence of MGMT methylation This study highlights the importance of assessing concurrent promoter methylation and checking its correlation with survival status among HGG.