Radzak, Siti Muslihah Abd
(2020)
Mitochondrial microsatellite genomic instability and brafv600e mutation in central nervous system tumors.
Masters thesis, Universiti Sains Malaysia.
Abstract
The central nervous system tumor is known as one of the fatal cancers
worldwide. The accumulation of multiple genetic alterations of the nuclear and
mitochondrial genome is believed to be engaged in brain tumorigenesis. Mitochondrial
microsatellite instability (mtMSI) is a change in repetitive sequences of the
mitochondrial genome, has been described as a high occurrence in several human
cancers. Meanwhile, the BRAFV600E is the most prevalent mutated nuclear oncogene
that has been identified in multiple malignancies. Nevertheless, mtMSI and
BRAFV600E mutation in brain tumor cases have not been reported in Malaysia, so far.
Therefore, this study aims to determine the mtMSI status and BRAFV600E mutation in
a series of Malay patients with brain tumors and to evaluate their association with
clinicopathological features. The mtMSI alterations and BRAFV600E mutations were
examined in a total of 50 paired brain tumor tissues and blood samples. The mtMSI
status was analysed using mtMSI specific primers and the results were compared with
the revised Cambridge References Sequences (rCRS). For the analysis of the
BRAFV600E mutation, the PCR-RLFP assay was used for sequence variation, followed
by direct sequencing and aligned using BLAST from the NCBI site. The results
revealed eight mtMSI alterations were detected in D310 and D16184 of the
displacement loop (D-loop) region (16%). Of these, one alteration C5TC4>C8TC in the
D16184 region has not been previously reported in the MITOMAP database identified
in this study. No association was found between mtMSI status and clinicopathological
data. Additionally, BRAFV600E mutation has been detected in 11 out of 50 patients
(22%). Similarly, no significant association between clinical features with BRAFV600E
mutation observed in this study. The correlation between mtMSI status and BRAFV600E
mutation also was analysed, however, no association identified between both
alterations in all screened patients. This study provides insights into mitochondrial
genome instability and BRAF mutation of brain tumor patients. A more detailed
analysis involving a large number of patients is needed to establish the exact role of
these genetic alterations in brain tumor cases in the Malay population.
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