Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Hu, Liwen; Yao, Xinyue; Shen, Yi

doi:10.1038/srep35859

Cited by 74 publications

(74 citation statements)

References 69 publications

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“…The combinations of the ingredients are altered according to individual preferences and it is preferred to be consumed in combination with zarda and gutkha. [33][34][35] The habit of betel quid chewing, cigarette smoking, gutkha, 36 zarda, 37 Khaini (chewing tobacco with lime), 38 alcohol along with cigarette smoking, and closed kitchen setup (minimal ventilation) with the use of traditional firewood for cooking are considered to be one of the potential risk factors responsible for HNSCC. 39 Tobacco consumption by cigarette smoking as well as chewing is also considered in development of HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India

et al. 2017

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Head and neck squamous cell carcinoma is the most commonly diagnosed cancer worldwide. The lifestyle, food habits, and customary practices manifest the Northeast Indian population toward higher susceptibility to develop head and neck squamous cell carcinoma. Here, we have investigated the association of smoke and smokeless tobacco, and alcohol with copy number variation of cell-free mitochondrial DNA and cell-free nuclear DNA in cases and controls. Cell-free DNA from plasma was isolated from 50 head and neck squamous cell carcinoma cases and 50 controls with informed written consent using QIAamp Circulating Nucleic Acid Kit. Real-time polymerase chain reaction was done for copy number variation in cell-free mitochondrial DNA and cell-free nuclear DNA. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic application between the two study groups using clinicopathological parameters. The levels of cell-free nuclear DNA and cell-free mitochondrial DNA of cases in association with smoke and smokeless tobacco, alcohol with smoking (p < 0.05) were significantly higher (p < 0.01 and p < 0.001, respectively) than controls. Using receiver operating characteristic curve analysis between head and neck squamous cell carcinoma cases and controls, we distinguished cell-free mitochondrial DNA (cutoff: 19.84 raw Ct; sensitivity: 84%; specificity: 100%; p < 0.001) and cell-free nuclear DNA (cutoff: 463,282 genomic equivalent/mL; sensitivity: 53%; specificity: 87%; p < 0.001). The copy number variation in cases (cell-free nuclear DNA: 5451.66 genomic equivalent/mL and cell-free mitochondrial DNA: 29,103,476.15 genomic equivalent/mL) and controls (cell-free nuclear DNA: 1650.9 genomic equivalent/mL and cell-free mitochondrial DNA: 9,189,312.54 genomic equivalent/mL), respectively. Our result indicates that the cell-free mitochondrial DNA content is highly associated with smoke and smokeless tobacco, betel quid chewing, and alcohol which shows greater promises, holding the key characteristics of diagnostic biomarkers, that is, minimal invasiveness, high specificity, and sensitivity.

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Section: Discussionmentioning

confidence: 99%

Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India

et al. 2017

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“…Metabolic reprograming is one of the key hallmarks of cancer (Ward and Thompson 2012), and mtDNA copy number has been reported to correlate with cancer invasiveness and overall patient outcomes (Chen et al 2016;Hu et al 2016). In addition, it has been suggested that lower levels of mtDNA in certain cancers may reflect a more stem-like metabolic program and be important in cancer stem cell biology (Lee et al 2015;Menendez 2015).…”

Section: Downloaded Frommentioning

confidence: 99%

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution

et al. 2019

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Mitochondria are involved in a number of diverse cellular functions, including energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation, and motility, as well as free radical generation. Mitochondrial DNA (mtDNA) is present at hundreds to thousands of copies per cell in a tissue-specific manner. mtDNA copy number also varies during aging and disease progression and therefore might be considered as a biomarker that mirrors alterations within the human body. Here, we present a new quantitative, highly sensitive droplet digital PCR (ddPCR) method, droplet digital mitochondrial DNA measurement (ddMDM), to measure mtDNA copy number not only from cell populations but also from single cells. Our developed assay can generate data in as little as 3 h, is optimized for 96-well plates, and also allows the direct use of cell lysates without the need for DNA purification or nuclear reference genes. We show that ddMDM is able to detect differences between samples whose mtDNA copy number was close enough as to be indistinguishable by other commonly used mtDNA quantitation methods. By utilizing ddMDM, we show quantitative changes in mtDNA content per cell across a wide variety of physiological contexts including cancer progression, cell cycle progression, human T cell activation, and human aging.

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“…The relative quantifications employed by most mtDNA investigations make comparisons between different studies difficult to interpret, often producing conflicting results. Additionally, both PCR efficiency (Regier and Frey 2010;Hu et al 2016) and the manner in which DNA is isolated (Andreu et al 2009;Malik et al 2011) present hurdles to understand the roles of mtDNA copy number during aging and disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…Metabolic reprograming is one of the key hallmark of cancer (Ward and Thompson 2012) and mtDNA copy number has been reported to correlate with cancer invasiveness and overall patient outcomes (Chen et al 2016;Hu et al 2016). In addition, it has been suggested that lower levels of mtDNA in certain cancers may reflect a more stem-like metabolic program and be important in cancer stem cell biology (Lee et al 2015;Menendez 2015).…”

Section: Detection Of Mtdna In a Variety Of Human Cells By Ddmdmmentioning

confidence: 99%

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single cell resolution: a focus on aging and cancer

O’Hara

Tedone

Ludlow

et al. 2019

Preprint

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Mitochondria are involved in a number of diverse cellular functions, including energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation and motility as well as free radical generation. Mitochondrial DNA (mtDNA) is present at hundreds to thousands of copies per cell in a tissue-specific manner. Importantly, mtDNA copy number also varies during aging and disease progression and therefore might be considered as a biomarker that mirrors alterations within the human body. Here we present a new quantitative, highly sensitive droplet digital PCR (ddPCR) method (ddMDM; droplet digital mitochondrial DNA measurement) to measure mtDNA copy number not only from cell populations but also from single cells. Our developed assay can generate data in as little as 3 hours, is optimized for 96-well plates and also allows the direct use of cell lysates without the need for DNA purification or nuclear reference genes. Importantly, we show that ddMDM is able to detect differences between samples whose mtDNA copy number was close enough as to be indistinguishable by other commonly used mtDNA quantitation methods. By utilizing ddMDM, we show quantitative changes in mtDNA content per cell across a wide variety of physiological contexts including cancer progression, cell cycle progression, human T cell activation, and human aging.

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Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Cited by 74 publications

References 69 publications

Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India

Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single cell resolution: a focus on aging and cancer

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