Brain Tumor Res Treat.  2018 Apr;6(1):31-38. 10.14791/btrt.2018.6.e5.

Mitochondrial 10398A>G NADH-Dehydrogenase Subunit 3 of Complex I Is Frequently Altered in Intra-Axial Brain Tumors in Malaysia

• Mohamed Yusoff AA
• Zulfakhar
• Mohd Khair SZN
• Wan Abdullah WS
• Abdullah J
• Idris Z

• KMID: 2410235
• DOI: http://doi.org/10.14791/btrt.2018.6.e5

Abstract

BACKGROUND
Mitochondria are major cellular sources of reactive oxygen species (ROS) generation which can induce mitochondrial DNA damage and lead to carcinogenesis. The mitochondrial 10398A>G alteration in NADH-dehydrogenase subunit 3 (ND3) can severely impair complex I, a key component of ROS production in the mitochondrial electron transport chain. Alteration in ND3 10398A>G has been reported to be linked with diverse neurodegenerative disorders and cancers. The aim of this study was to find out the association of mitochondrial ND3 10398A>G alteration in brain tumor of Malaysian patients.
METHODS
Brain tumor tissues and corresponding blood specimens were obtained from 45 patients. The ND3 10398A>G alteration at target codon 114 was detected using the PCR-RFLP analysis and later was confirmed by DNA sequencing.
RESULTS
Twenty-six (57.8%) patients showed ND3 10398A>G mutation in their tumor specimens, in which 26.9% of these mutations were heterozygous mutations. ND3 10398A>G mutation was not significantly correlated with age, gender, and histological tumor grade, however was found more frequently in intra-axial than in extra-axial tumors (62.5% vs. 46.2%, p < 0.01).
CONCLUSION
For the first time, we have been able to describe the occurrence of ND3 10398A>G mutations in a Malaysian brain tumor population. It can be concluded that mitochondrial ND3 10398A>G alteration is frequently present in brain tumors among Malaysian population and it shows an impact on the intra-axial tumors.

Keyword

Brain tumor; Mitochondrial DNA; ND3 A10398G mutation; Malaysia

MeSH Terms

Brain Neoplasms*
Brain*
Carcinogenesis
Codon
DNA, Mitochondrial
Electron Transport
Humans
Malaysia*
Mitochondria
Neurodegenerative Diseases
Reactive Oxygen Species
Sequence Analysis, DNA
Codon
DNA, Mitochondrial
Reactive Oxygen Species

Figure

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  Fig. 1 Agarose gel electrophoresis of mitochondrial ND3 PCR products. Amplification products of the expected size of 422-bp was detected in 2% agarose gels. Lane M, 100 bp DNA marker; Lane 1, negative control; Lane 2–7, tumor samples.

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  Fig. 2 PCR-RFLP analysis of ND3 (A10398G) mutations in brain tumor patients. Fragment of ND3 gene digested with DdeI (Hpy-F3I) enzyme. Lane M, 100 bp DNA marker; Lane 1, undigest product (422-bp); Lane 2, normal sample; Lane 3–7, tumor samples. Three bands at 213-bp, 130-bp & 80-bp indicate a wild type. Four bands at 175-bp, 130-bp, 80-bp & 38-bp indicate a homozygous mutation. Five bands at 213-bp, 175-bp, 130-bp, 80-bp & 38-bp indicate a heterozygous mutation.

• 

  Fig. 3 Representative sequencing results showing example of mitochondrial ND3 mutations in brain tumor tissue sample. Chromatograms show a mutation of A to G transition at nucleotide position 10398.

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  Fig. 4 The pie charts depict the percentages of ND3 10398A>G mutations in brain tumor patients. A: Mutation vs. wild type. B: Heterozygous mutations vs. homozygous mutations.

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