Mitochondria are cellular machines essential for energy production. The biogenesis of mitochondria is a highly complex and it depends on the coordination of the nuclear and mitochondrial genome. Mitochondrial DNA (mtDNA) mutations and deletions are suspected to be associated with carcinogenesis. The most described mtDNA deletion in various human cancers is called the 4977-bp common deletion (mDNA4977) and it has been explored since two decades. In spite of that, its implication in carcinogenesis still unknown and its predictive and prognostic impact remains controversial. This review article provides an overview of some of the cellular and molecular mechanisms underlying mDNA4977 formation and a detailed summary about mDNA4977 reported in various types of cancers. The current knowledges of mDNA4977 as a prognostic and predictive marker are also discussed.

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.

AIM:To determine the mitochondrial microsatellite instability (mtMSI) status in a series of Malaysian patients with brain tumors. Furthermore, we analyzed whether the mtMSI status is associated with the clinicopathological features of the patients. MATERIAL and METHODS:Forty fresh frozen tumor tissues along with blood samples of brain tumor patients were analyzed for mtMSI by PCR amplification of genomic DNAs, and the amplicons were directly sequenced in both directions using Sanger sequencing. RESULTS:Microsatellite analysis revealed that 20% (8 out of 40) of the tumors were mtMSI positive with a total of 8 mtMSI changes. All mtMSI markers were detected in D310 and D16184 of the D-loop region. Additionally, no significant association was observed between mtMSI status and clinicopathological features. CONCLUSION:The variations, specifically the mtMSI, suggest that the mitochondrial DNA (mtDNA) can be targeted for genomic alteration in brain tumors. Therefore, the specific role of mtDNA alteration in brain tumor development and prognosis requires further investigation.

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.

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.