Original scientific paper
https://doi.org/10.3325/cmj.2024.65.111
The effect of somatic mutations in mitochondrial DNA on the survival of patients with primary brain tumors
Siti Zulaikha Nashwa Mohd Khair
; Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
Siti Muslihah Ab Radzak
; Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
Zamzuri Idris
; Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
Anani Aila Mat Zin
; Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
Wan Muhamad Amir Wan Ahmad
; School of Dental Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
Abdul Aziz Mohamed Yusof
; Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
*
* Corresponding author.
Abstract
Aim To assess the presence of mitochondrial (mt) DNA
somatic mutations, determine the relationship between
clinicopathological characteristics and mutations, and assess the survival outcomes in Malay patients with primary
brain tumors.
Methods The study enrolled 54 patients with primary
brain tumors. DNA extracted from paired tissue and blood
samples was subjected to Sanger sequencing to identify
alterations in the entire mtDNA. The associations between
clinicopathological characteristics and mutations were
evaluated. Cox-regression multivariate analysis was conducted to identify factors significantly associated with survival, and Kaplan-Meier analysis was used to compare the
survival of patients with and without mutations.
Results Overall, 29.6% of the patients harbored 19 somatic mutations distributed across 15 loci within the mtDNA.
Notably, 36.8% of these mutations were not previously
documented in MITOMAP. One newly identified mutation
caused a frameshift in the ATPase6 gene, resulting in a premature stop codon. Three mutations were classified as deleterious in the MitImpact2 database. Overall, 1097 mtDNA
polymorphisms were identified across 331 different locations. Patients with mutations exhibited significantly shorter survival than patients without mutations.
Conclusions mtDNA mutations negatively affected the
survival outcomes of Malaysian patients with primary brain
tumors. However, studies with larger samples are needed
to confirm the association between mutation burden and
survival rates.
Keywords
Hrčak ID:
331942
URI
Publication date:
30.4.2024.
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