Total DNA methylation profile in assessing the MGMT gene promoter status in malignant gliomas

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OBJECTIVE

To analyze the DNA methylation signal intensity in the MGMT gene in samples of malignant gliomas and identify the most significant genomic positions for calculating the MGMT gene promoter status for further improvement of diagnostics and prediction of therapeutic options in patients with malignant gliomas.

MATERIAL AND METHODS

The study is based on 43 samples (frozen tissue or paraffin blocks) from patients with malignant gliomas. Tumor DNA samples were prepared using the Illumina Infinium MethylationEPIC BeadChip Kit and the Illumina Next-Seq 550 Sequencing System platform. DNA methylation profiles were analyzed using computational algorithms in the R language, specialized libraries minfi and mgmtstp27, as well as basic statistical functions in the Rstudio environment.

RESULTS

We established the MGMT gene promoter status in 43 samples of malignant gliomas considering total DNA methylation profile. In 24 samples (55%), the MGMT gene promoter was methylated. We compared methylation signal in certain CpG islands in groups with methylated and unmethylated MGMT gene promoters and identified the most significant positions for further improvement of data analysis algorithm.

CONCLUSION

These data demonstrate the possibilities and prospects for further improvement of algorithm for analysis of the MGMT gene promoter status based on total DNA methylation profile in patients with malignant gliomas as an alternative to methyl-specific PCR. Our results are consistent with data of other neuro-oncology researchers. Indeed, computational methods like MGMT-STP27 are quite powerful and can be used in scientific and clinical practice to assess prognosis and make decisions about chemotherapy with alkylating agents.

Keywords:

malignant gliomas

molecular diagnostics

epigenetics of CNS tumors

DNA methylation

MGMT gene promoter status

Illumina EPIC Methylation microarray

Authors:

Petrova E.I.

Burdenko Neurosurgical Center

ORCID: 0000-0003-2498-4713

Galstyan S.A.

Burdenko Neurosurgical Center

ORCID: 0000-0001-9953-6654

Telysheva E.N.

Burdenko Neurosurgical Center

ORCID: 0000-0002-0370-8667

Ryzhova M.V.

Burdenko Neurosurgical Center

ORCID: 0000-0001-7206-6365

Received:

23.08.2023

Accepted:

14.09.2023

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