Mitochondrial microsatellite genomic instability and brafv600e mutation in central nervous system tumors
Year: 2020
Type: dissertation
Study design: Observational Study
Abstract: The central nervous system tumor is known as one of the fatal cancers \nworldwide. The accumulation of multiple genetic alterations of the nuclear and \nmitochondrial genome is believed to be engaged in brain tumorigenesis. Mitochondrial \nmicrosatellite instability (mtMSI) is a change in repetitive sequences of the \nmitochondrial genome, has been described as a high occurrence in several human \ncancers. Meanwhile, the BRAFV600E is the most prevalent mutated nuclear oncogene \nthat has been identified in multiple malignancies. Nevertheless, mtMSI and \nBRAFV600E mutation in brain tumor cases have not been reported in Malaysia, so far. \nTherefore, this study aims to determine the mtMSI status and BRAFV600E mutation in \na series of Malay patients with brain tumors and to evaluate their association with \nclinicopathological features. The mtMSI alterations and BRAFV600E mutations were \nexamined in a total of 50 paired brain tumor tissues and blood samples. The mtMSI \nstatus was analysed using mtMSI specific primers and the results were compared with \nthe revised Cambridge References Sequences (rCRS). For the analysis of the \nBRAFV600E mutation, the PCR-RLFP assay was used for sequence variation, followed \nby direct sequencing and aligned using BLAST from the NCBI site. The results \nrevealed eight mtMSI alterations were detected in D310 and D16184 of the \ndisplacement loop (D-loop) region (16%). Of these, one alteration C5TC4>C8TC in the \nD16184 region has not been previously reported in the MITOMAP database identified \nin this study. No association was found between mtMSI status and clinicopathological \ndata. Additionally, BRAFV600E mutation has been detected in 11 out of 50 patients \n(22%). Similarly, no significant association between clinical features with BRAFV600E \nmutation observed in this study. The correlation between mtMSI status and BRAFV600E \nmutation also was analysed, however, no association identified between both \nalterations in all screened patients. This study provides insights into mitochondrial \ngenome instability and BRAF mutation of brain tumor patients. A more detailed \nanalysis involving a large number of patients is needed to establish the exact role of \nthese genetic alterations in brain tumor cases in the Malay population.
Author: Radzak, Siti Muslihah Abd
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3119153742