Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 14;13(6):999.
doi: 10.3390/jpm13060999.

MGMT Promoter Methylation: Prognostication beyond Treatment Response

Keyoumars Ashkan  1 , Asfand Baig Mirza  1 , Christos Soumpasis  1 , Christoforos Syrris  1 , Dimitrios Kalaitzoglou  1 , Chaitanya Sharma  2 , Zachariah Joseph James  2 , Abbas Khizar Khoja  2 , Razna Ahmed  2 , Amisha Vastani  1 , James Bartram  1 , Kazumi Chia  1 , Omar Al-Salihi  3 , Angela Swampilai  3 , Lucy Brazil  3 , Ross Laxton  4 , Zita Reisz  4 , Istvan Bodi  4 , Andrew King  4 , Richard Gullan  1 , Francesco Vergani  1 , Ranjeev Bhangoo  1 , Safa Al-Sarraj  1 , Jose Pedro Lavrador  1
Affiliations

MGMT Promoter Methylation: Prognostication beyond Treatment Response

Keyoumars Ashkan et al. J Pers Med. .

Abstract

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Keywords: 5-ALA; GBM; MGMT; glioblastoma; methylation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Highly methylated MGMT promoter methylation (37.93%): Axial (A), Sagittal (B) and Coronal (C) views of T1-Gadolinium weighted image showing a right frontal contrast-enhancing lesion in the ventral premotor cortex. Intraoperative image of the tumour invading the cortical surface (subdural strip in place for intraoperative neuromonitoring) (D). Tumour specimen under white light (E) and BLUE 400 Filter showing non-homogenous moderate 5-ALA fluorescence (F).
Figure 2
Figure 2
Low methylated MGMT promoter methylation (4.5%): Axial (A), Coronal (D) and Sagittal (E) views of T1-Gadolinium weighted image showing a right frontal contrast-enhancing lesion within the primary motor and sensory cortices. 3D reconstruction of the tumour (white) and lower limb (green) and upper limb (red) corticospinal tract fibres embracing the lesion (B). Intraoperative image of the tumour invading the cortical surface with augmented reality for the corticospinal tract fibres (C). Tumour visualized under white light (C) and BLUE 400 filter showing homogenous and bright fluorescence (F). Number 1 and 2 are cortical areas with positive motor activation for upper limb with high frequency stimulation paradigm.
Figure 3
Figure 3
Correlation between percentage of MGMT promoter methylation and the extent of resection.
Figure 4
Figure 4
Kaplan–Meier curves illustrating the different survival curves according to different categories of MGMT promotor methylation, p = 0.008.
See this image and copyright information in PMC

References

    1. Louis D.N., Perry A., Reifenberger G., von Deimling A., Figarella-Branger D., Cavenee W.K., Ohgaki H., Wiestler O.D., Kleihues P., Ellison D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary. Acta Neuropathol. 2016;131:803–820. doi: 10.1007/s00401-016-1545-1. - DOI - PubMed
    1. Tamimi A.F., Juweid M. Epidemiology and Outcome of Glioblastoma. Exon Publ. 2017:143–153. doi: 10.15586/codon.glioblastoma.2017.ch8. - DOI - PubMed
    1. Ostrom Q.T., Gittleman H., Farah P., Ondracek A., Chen Y., Wolinsky Y., Stroup N.E., Kruchko C., Barnholtz-Sloan J.S. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2006–2010. Neuro-Oncology. 2013;15((Suppl. 2)):ii1–ii56. doi: 10.1093/neuonc/not151. - DOI - PMC - PubMed
    1. Koshy M., Villano J.L., Dolecek T.A., Howard A., Mahmood U., Chmura S.J., Weichselbaum R.R., McCarthy B.J. Improved Survival Time Trends for Glioblastoma Using the SEER 17 Population-Based Registries. J. Neurooncol. 2012;107:207–212. doi: 10.1007/s11060-011-0738-7. - DOI - PMC - PubMed
    1. Grochans S., Cybulska A.M., Simińska D., Korbecki J., Kojder K., Chlubek D., Baranowska-Bosiacka I. Epidemiology of Glioblastoma Multiforme–Literature Review. Cancers. 2022;14:2412. doi: 10.3390/cancers14102412. - DOI - PMC - PubMed