Mitochondrial DNA copy number as a prognostic marker is age-dependent in adult glioblastoma

Sourty, Baptiste; Dardaud, Laure-Marie; Bris, Céline; Desquiret-Dumas, Valérie; Boisselier, Blandine; Basset, Laëtitia; Figarella‐Branger, Dominique; Morel, Alain; Sanson, Marc; Procaccio, Vincent; Rousseau, Audrey

doi:10.1093/noajnl/vdab191

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…This observation aligns with previous studies that highlighted the correlation between increased mtDNA copy numbers and improved overall survival in GBM patients. 14 , 15 Additionally, our observations revealed that elevated mtDNA content displayed a favorable prognosis in high-grade tumor patients. A prior study similarly emphasized the significance of the increased mtDNA content in the survival of high-grade glioma patients.…”

Section: Discussionsupporting

confidence: 55%

Mitochondrial Deoxyribonucleic Acid Copy Number Elevation As a Predictor for Extended Survival and Favorable Outcomes in High-Grade Brain Tumor Patients: A Malaysian Study

Radzak,

Mohd Khair,

Idris

et al. 2024

The Eurasian Journal of Medicine

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Background: Investigating the role of mitochondrial DNA (mtDNA) alterations and their impact on brain tumor progression remains a significant focus in cancer research. The research aimed to explore the specific contributions of mtDNA copy number changes and their correlations with patient survival, large mtDNA deletions, and TFAM mutations in brain tumor patients. Methods: A total of 41 patients with confirmed brain tumors underwent DNA extraction from both tumor tissues and blood samples. The relative mtDNA copy number in comparison to the nuclear genome was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Long-range PCR assessed large-scale mtDNA deletions, and Sanger sequencing was applied to detect exon 4 TFAM mutations. Results: Analysis revealed significantly increased mtDNA copy numbers in brain tumor tissues (80.5%) compared to matched blood samples ( P < .001). Median delta Ct (∆Ct) values were 7.35 in cancerous tissues and 11.81 in blood ( P < .001), with median relative mtDNA content of 0.0123 and 0.0006, respectively ( P < .001). Patients with higher mtDNA copy numbers experienced longer overall survival periods ( P = .045) and notably favorable outcomes, particularly in high-grade tumor cases ( P = .016). Furthermore, a single-nucleotide deletion was identified in exon 4 of TFAM in a patient with glioblastoma IV, while no large-scale mtDNA deletions were found in brain tumor patients. Conclusion: Our study strongly supports the role of increased mtDNA copy numbers as a reliable predictor for improved survival and positive outcomes in high-grade brain tumor patients.

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Section: Discussionsupporting

confidence: 55%

Mitochondrial Deoxyribonucleic Acid Copy Number Elevation As a Predictor for Extended Survival and Favorable Outcomes in High-Grade Brain Tumor Patients: A Malaysian Study

Radzak,

Mohd Khair,

Idris

et al. 2024

The Eurasian Journal of Medicine

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“…Similarly, mtDNA depletion was associated with cancer progression to a more malignant phenotype with adverse prognosis in glioblastoma patients [ 30 , 35 ]. mtDNA copy number has been a novel prognostic biomarker in GBM [ 36 , 37 ]. Additionally, we observed in the present study that rotenone-induced mitochondrial dysfunction promoted TMZ resistance in glioblastoma cells and that the susceptibility to TMZ treatment was increased with the prolongation of rotenone treatment ( Figure S9a ).…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Analyses Reveal Mitochondrial Dysfunction Contributing to Temozolomide Resistance in Glioblastoma Cells

Zhang,

Chen,

Liu

et al. 2023

Biomolecules

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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with poor prognosis. Temozolomide (TMZ) is the standard chemotherapy for glioblastoma treatment, but TMZ resistance significantly compromises its efficacy. In the present study, we generated a TMZ-resistant cell line and identified that mitochondrial dysfunction was a novel factor contributing to TMZ resistance though multi-omics analyses and energy metabolism analysis. Furthermore, we found that rotenone treatment induced TMZ resistance to a certain level in glioblastoma cells. Notably, we further demonstrated that elevated Ca2+ levels and JNK–STAT3 pathway activation contributed to TMZ resistance and that inhibiting JNK or STAT3 increases susceptibility to TMZ. Taken together, our results indicate that co-administering TMZ with a JNK or STAT3 inhibitor holds promise as a potentially effective treatment for glioblastoma.

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“…diagnozy [38]. Mutacje IDH1/IDH2 determinują zatem lepsze rokowanie u pacjentów ze zdiagnozowanym glejakiem.…”

Section: Mutacje W Obrębie Idh1/idh2unclassified

Genetyczne i molekularne podłoża rozwoju glejaka

Panek,

Jezela-Stanek

2024

Postepy Biochem

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Stage IV glioblastoma is the most frequently diagnosed and the worst prognosis tumor of the central nervous system (CNS). Patients suffering from this type of cancer usually survive several months with the use of surgical treatment, radiotherapy and chemotherapy. The development of glioblastoma is determined by a number of mutations, the most common of which are the p16, p19, p53, pRB, PTEN, PDGFR, CDK4 and EGFR protein genes as well as the loss of heterozygosity on chromosomes 10, 17 and 19. The occurrence of mutations within the IDH1 and IDH2 genes and increased methylation of MGMT promoter improves patient survival, but few patients live more than 3 years after diagnosis. The most important cell signaling pathways in glioblastoma are PI3K/Akt/mTOR and Wnt/β-catenin, which play a key role in tumor cell function. However, these cells are highly resistant to anticancer drugs, including inhibitors of cell signaling pathways. Currently, the potential methods of effectively combating malignant gliomas are alternating electric field therapy and the implementation of new immunotherapeutic strategies.

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Mitochondrial DNA copy number as a prognostic marker is age-dependent in adult glioblastoma

Cited by 5 publications

References 51 publications

Mitochondrial Deoxyribonucleic Acid Copy Number Elevation As a Predictor for Extended Survival and Favorable Outcomes in High-Grade Brain Tumor Patients: A Malaysian Study

Mitochondrial Deoxyribonucleic Acid Copy Number Elevation As a Predictor for Extended Survival and Favorable Outcomes in High-Grade Brain Tumor Patients: A Malaysian Study

Multi-Omics Analyses Reveal Mitochondrial Dysfunction Contributing to Temozolomide Resistance in Glioblastoma Cells

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