Publication: Mitochondrial genome instability: its potential role in biomarker discovery for brain tumorigenesis
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Date
2017
Authors
Yusoff, Abdul Aziz Mohamed
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Abstract
Background: Mitochondria are major cellular sources of reactive oxygen species (ROS) generation
which can induce mitochondrial DNA (mtDNA) damage and lead to carcinogenesis. MtDNA 4,977-bp
deletion as well as alteration in mtDNA copy number have been implicated in various types of human
cancers. The aim of the present study was to find out the association of mtDNA 4,977-bp deletion and
mtDNA content in brain tumor from the Malaysian patients.
Methods: Brain tumor tissues and corresponding blood specimens were obtained from 50 patients. For
comparison, 40 blood samples of healthy controls were also included in this study. The mtDNA 4,977-
bp deletion was detected using the multiplex Polymerase chain reaction (PCR) analysis and later was
confirmed by direct DNA sequencing. Furthermore, the mtDNA content was analyzed by using a
quantitative real time PCR method.
Results: The mtDNA 4,977-bp deletion were observed in 24% (12 out of 50) of our patients. Presence
of the ND3 10398A>G mutation did not show significantly correlation with any of the evaluated
parameters such as patients age, gender and histological brain tumor types. Moreover, we found that
mtDNA copy number was significantly reduced in tumor tissues (13.49+9.32) compared to
corresponding blood samples (36.65±9.32). Our study also revealed that 28% of our patients (14 out of
50) were detected to have the 1DH1 c.395G>A (R132H) mutation and a significant association was
found with histological tumor types.
Conclusions: For the first time, we have been able to describe the occurrence of mtDNA 4,977-bp
deletion and decreased mtDNA content in a Malaysian brain tumor population. Deletion of mtDNA
4,977-bp could be classified as pathogenic mutation in connection with mutations in other
mitochondrial or nuclear genes as well as environmental factors in the development of various diseases
and cancers. We believe that mtDNA 4,977-bp deletion and mtDNA content determination may be
considered as potential diagnostic and prognostic biomarker among Malaysian population particularly
in those with brain tumors.
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Keywords
brain