Accumulation of mitochondrial dna microsatellite instability in malaysian patients with primary central nervous system tumors

Radzak, Siti Muslihah Abd; Khair, Zulaikha; Ahmad, Fadzil; Idris, Zamzuri; Yusoff, Abdul Aziz Mohamed

doi:10.5137/1019-5149.jtn.27893-20.4

Cited by 6 publications

(8 citation statements)

References 61 publications

(70 reference statements)

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“…Two different studies demonstrated the D310 detection in normal adjacent epithelial cells of breast [179] and gallbladder carcinomas [180], in conjunction with a mutation-carrying cancerous tissues. The D310 mtMSI was also observed in 12% of brain tumor patients [176], 34% in rectal carcinoma, and 38% in sigmoid or colorectal carcinoma [181].…”

Section: Mitochondrial Microsatellite Instability (Mtmsi)mentioning

confidence: 90%

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The Uprising of Mitochondrial DNA Biomarker in Cancer

2021

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Cancer is a heterogeneous group of diseases, the progression of which demands an accumulation of genetic mutations and epigenetic alterations of the human nuclear genome or possibly in the mitochondrial genome as well. Despite modern diagnostic and therapeutic approaches to battle cancer, there are still serious concerns about the increase in death from cancer globally. Recently, a growing number of researchers have extensively focused on the burgeoning area of biomarkers development research, especially in noninvasive early cancer detection. Intergenomic cross talk has triggered researchers to expand their studies from nuclear genome-based cancer researches, shifting into the mitochondria-mediated associations with carcinogenesis. Thus, it leads to the discoveries of established and potential mitochondrial biomarkers with high specificity and sensitivity. The research field of mitochondrial DNA (mtDNA) biomarkers has the great potential to confer vast benefits for cancer therapeutics and patients in the future. This review seeks to summarize the comprehensive insights of nuclear genome cancer biomarkers and their usage in clinical practices, the intergenomic cross talk researches that linked mitochondrial dysfunction to carcinogenesis, and the current progress of mitochondrial cancer biomarker studies and development.

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Section: Mitochondrial Microsatellite Instability (Mtmsi)mentioning

confidence: 90%

“…However, responsible mechanisms involving mtMSI are not much known [174]. Among all, the most frequently reported mtMSI is located in the D-loop region [176]. The D310 site is a mutational hotspot in primary tumors and described as a highly polymorphic homopolymeric C stretch [177].…”

Section: Mitochondrial Microsatellite Instability (Mtmsi)mentioning

confidence: 99%

The Uprising of Mitochondrial DNA Biomarker in Cancer

2021

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“…More recently, we detected mtMSI in 20% of a series of 40 primary brain tumours. We observed a total of 8 different alterations within 2 loci, D310 and D16184, of mtMSI markers [ 141 ].…”

Section: Other Cancersmentioning

confidence: 99%

Research highlights on contributions of mitochondrial DNA microsatellite instability in solid cancers – an overview

Yusoff¹,

Radzak²,

Khair³

2022

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Cancer has been broadly considered a genetic disease involving mutations in nuclear DNA and the mitochondrial genome (mtDNA). Mitochondria are essential bioenergetics and biosynthetic machinery found in most eukaryotic organisms. Thus, failure of their function is crucial for tumourigenesis, tumour cell growth, and metastasis. Mitochondrial dysregulation can occur as a consequence of molecular alterations in mtDNA, such as point mutations, deletions, inversions, microsatellite instability (MSI), and copy number variations. This review article aims to highlight the published research work on alterations in mtDNA, with a particular focus on mitochondrial MSI (mtMSI) in various types of solid cancers. Databases including PubMed, Scopus, and Google Scholar were searched for articles about mtMSI and its link to solid cancer published from 1990 till 2021. In this review, we briefly summarize the knowledge related to possible molecular mechanisms causing mtMSI formation and the available information on mtMSI frequency values in all main solid cancer types. Mutations in the mitochondrial genome are widely believed to have a broad impact across various cancers. Based on the available published data, mtMSI can act as a vital risk factor and a potential marker for cancer progression. Further research is required to unravel the role of mtMSI in tumourigenesis.

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“…These alterations substantially alter mitochondrial respiration capacity, other than stimulating a higher rate of oxidative stress and apoptosis ( 45 ). mtDNA mutations frequently occur within the hypervariable D-loop region, particularly in a homopolycytidine stretch or near the replication origins of the mtDNA H-strand ( 11 ). This crucial region possesses a triple-stranded DNA structure, which is severely liable to the persistent effect of oxidative insults, thus, possibly increasing the rate of mutations.…”

Section: Mtdna-cnmentioning

confidence: 99%

“…mtDNA is recognized to be highly unstable and liable to damage compared to the nuclear genome, due to the persistent exposure to oxidative attack coupled with deficient DNA repair machinery ( 11 ). As a result, mtDNA suffers from the formation of sequence alterations or depletion of mtDNA content, consequently leading to various disorders and cancer tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Insights regarding mitochondrial DNA copy number alterations in human cancer (Review)

et al. 2022

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Mitochondria are the critical organelles involved in various cellular functions. Mitochondrial biogenesis is activated by multiple cellular mechanisms which require a synchronous regulation between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). The mitochondrial DNA copy number (mtDNA-CN) is a proxy indicator for mitochondrial activity, and its alteration reflects mitochondrial biogenesis and function. Despite the precise mechanisms that modulate the amount and composition of mtDNA, which have not been fully elucidated, mtDNA-CN is known to influence numerous cellular pathways that are associated with cancer and as well as multiple other diseases. In addition, the utility of current technology in measuring mtDNA-CN contributes to its extensive assessment of diverse traits and tumorigenesis. The present review provides an overview of mtDNA-CN variations across human cancers and an extensive summary of the existing knowledge on the regulation and machinery of mtDNA-CN. The current information on the advanced methods used for mtDNA-CN assessment is also presented.

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Accumulation of mitochondrial dna microsatellite instability in malaysian patients with primary central nervous system tumors

Cited by 6 publications

References 61 publications

The Uprising of Mitochondrial DNA Biomarker in Cancer

The Uprising of Mitochondrial DNA Biomarker in Cancer

Research highlights on contributions of mitochondrial DNA microsatellite instability in solid cancers – an overview

Insights regarding mitochondrial DNA copy number alterations in human cancer (Review)

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