Murali, Revathy
(2018)
The evaluation of 06-methylguanine-DNA-methyltransferase (MGMT) gene methylation status among Hospital Universiti Sains Malaysia glioma patients.
Masters thesis, Universiti Sains Malaysia.
Abstract
Growing evidences demonstrate the understanding of the biomarkers and it
significantly increased our current perception of gliomagenesis, prognostic evaluation,
and treatment planning for the patients. For instance, identification of the promoter
methylation status of O6-methylguanine-DNA-methyltransferase (MGMT) gene
encodes MGMT, a protein with DNA repair activity may improve the efficacy of
current standard care in glioma as the methylation status has been recently introduced
to be a predictive biomarker for stratification of the treatment plan. To further
understand the roles of MGMT, we aimed to evaluate the MGMT promoter methylation
status of glioma patients in Hospital USM. In this study, 41 samples of paraffinembedded
glioma tissue (FFPE) were obtained based on their grading from Grade II
(n = 11), III (n = 10) and IV (n = 20). Subsequently, DNA extraction and methylation
status was validated by methylation-specific PCR (MSP) method using two pairs of
primers specifically targeting the unmethylated (UM) and methylated (M) regions of
the MGMT gene, respectively. MSP results identified high intratumoral heterogeneity
of the samples in all grades of the tumours. In Grade II glioma, 9.1% were M and
90.9% were combination of UM and M. Moreover, Grade III glioma indicated 50% M
and combination of UM and M, respectively. Besides, Grade IV glioma exhibited 15%
were UM, 30% were M and 55% were both UM and M. Nevertheless, analysis using
Fisher’s exact test found no statistical association of the MGMT methylation status
with any of the tested clinicopathological parameters such as tumour grade, age,
gender, and race of the patients (p > 0.05). In conclusion, this study found frequent
MGMT methylation, regardless of the tumour grade, age, gender and race of the glioma
patients at Hospital USM. Moreover, the occurrence of MGMT combination status in
all grades of gliomas suggested intratumoral heterogeneity of the tumour. Besides
imparting intratumoral diversity, it may also indicate possible challenges in defining
personalized treatment based on the epigenetic status of MGMT.
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