High mitochondrial DNA copy number is associated with longer survival in young patients with glioblastoma

Dardaud, Laure-Marie; Bris, Céline; Desquiret-Dumas, Valérie; Boisselier, Blandine; Tabouret, Émeline; Mokhtari, Karima; Figarella‐Branger, Dominique; Rousseau, Audrey; Procaccio, Vincent

doi:10.1093/neuonc/noz072

Cited by 10 publications

(11 citation statements)

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“…We did not separately analyze the mtDNA content by the histological subtype was that there were two few papillary and habdoid meningioma patients in the cohort which would lead to statistical bias. Zhang et al revealed that in their series of 151 glioma patients, mtDNA content was associated with recurrent status in glioma, which was confirmed by two recent studies (40,41). In breast cancer, Marjolein reported low mtDNA content was more prevalent in ER positive breast cancers (20).…”

Section: Discussionmentioning

confidence: 81%

High Tumor Mitochondrial DNA Content Correlates With an Improved Patient's Outcome in WHO Grade III Meningioma

et al. 2020

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Background: Studies have shown mitochondrial genome content (mtDNA content) varies in many malignancies. However, its distribution and prognostic values in high-grade meningioma remain largely unknown. In this retrospective study, we sought to assess a putative correlation between the mtDNA content and clinical characteristics. Methods: Mitochondrial DNA was extracted from 87 World Health Organization grade III meningioma samples using a qPCR method. The distribution of mtDNA content in WHO grade III meningioma and its correlations with clinical variables were assessed. Furthermore, we prognostic values were also determined. Results: Mean mtDNA content was 617.7 (range, 0.8-3000). There was no mtDNA distribution difference based on the histological subtypes (P = 0.07). Tumors with preoperative radiation were associated with lower mtDNA content (P = 0.041), whereas no correlations with other clinical variables were observed. A high mtDNA content was associated with significantly better PFS (P = 0.044) and OS (P = 0.019). However, in patients who received postoperative radiotherapy, low mtDNA content was associated with better PFS (P = 0.028), while no difference in OS was observed (P = 0.272). Low mtDNA content was also associated with better OS and PFS in subgroups of patients with ER negative status (PFS, P = 0.002; OS, P = 0.002). Conclusions: Consistent with other tumors, high mtDNA content was associated with better outcome in WHO grade III meningioma in our cohort. However, for patients who received post-operative radiation therapy, low mtDNA content was associated with better PFS. These findings suggest that mtDNA content may further be explored as a potential biomarker for high-grade meningioma patients and for those who received postoperative radiation therapy.

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Section: Discussionmentioning

confidence: 81%

High Tumor Mitochondrial DNA Content Correlates With an Improved Patient's Outcome in WHO Grade III Meningioma

et al. 2020

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“…Of the 232 cases included, 67 have already been reported. 11 The whole cohort is presented in Supplementary Material S1 .…”

Section: Methodsmentioning

confidence: 99%

“… 8–10 We have previously shown that high mtDNA levels were significantly associated with longer overall survival (31.8 months vs 12.9 months; P = .013) in young adult GBM patients (≥18 years-old and < 40 years-old; n = 67) strongly suggesting that mtDNA copy number may represent a novel prognostic marker in GBM. 11 We assessed the correlation between mtDNA levels and prognosis in a larger cohort of GBM patients with a wider age range, older patients being the most affected by the disease.…”

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confidence: 99%

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

Sourty

Dardaud

Bris

et al. 2022

Neuro-Oncology Advances

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Background Glioblastoma (GBM) is the most common and aggressive form of glioma. GBM frequently displays chromosome (chr) 7 gain, chr 10 loss and/or EGFR amplification (chr7+/chr10-/EGFRamp). Overall survival (OS) is 15 months after treatment. In young adults, IDH1/2 mutations are associated with longer survival. In children, histone H3 mutations portend a dismal prognosis. Novel reliable prognostic markers are needed in GBM. We assessed the prognostic value of mitochondrial DNA (mtDNA) copy number in adult GBM. Methods mtDNA copy number was assessed using real-time quantitative PCR in 232 primary GBM. Methylation of POLG and TFAM genes, involved in mtDNA replication, was assessed by bisulfite-pyrosequencing in 44 and 51 cases, respectively. Results Median age at diagnosis was 56.6 years-old and median OS, 13.3 months. 153/232 GBM (66 %) displayed chr7+/chr10-/EGFRamp, 23 (9.9 %) IDH1/2 mutation, 3 (1.3 %) H3 mutation and 53 (22.8 %) no key genetic alterations. GBM were divided into two groups, “Low” (n = 116) and “High” (n = 116), according to the median mtDNA/nuclear DNA ratio (237.7). There was no significant difference in OS between the two groups. By dividing the whole cohort according to the median age at diagnosis, OS was longer in the “High” vs “Low” subgroup (27.3 vs 15 months, p = 0.0203) in young adult GBM (n = 117) and longer in the “Low” vs “High” subgroup (14.5 vs 10.2 months, p = 0.0116) in older adult GBM (n = 115). POLG was highly methylated, whereas TFAM remained unmethylated. Conclusion mtDNA copy number may be a novel prognostic biomarker in GBM, its impact depending on age.

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“…Even so, mtDNA content in each cell type is kept within a constant range to maintain cellular energy levels and, thus, cell function [ 59 ]. However, changes in mtDNA content are reportedly occurring at early stages of carcinogenesis [ 62 , 63 ], as a reflection of essential mutations for neoplastic transformation [ 62 ], leading to alterations in OXPHOS and, consequently, ATP production [ 64 , 65 ].…”

Section: Mitochondrial Dna Alterations In Glioblastomamentioning

confidence: 99%

“…Body fluids such as blood, urine, saliva, and CSF can be used to detect cfmtDNA that are linked to GBM prognosis, response to treatment, and tumor recurrence [ 63 , 65 , 67 ]. In that sense, as tumoral mtDNA content variation is correlated with the patient’s prognosis, variations in mtDNA copy number in peripheral blood may be used as a biomarker for diagnosis [ 12 , 59 ] as well as prognosis [ 75 ].…”

Section: Mtdna Alterations and Liquid Biopsiesmentioning

confidence: 99%

Mitochondrial DNA Alterations in Glioblastoma (GBM)

Barros

Pinheiro

Borges

2021

IJMS

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Glioblastoma (GBM) is an extremely aggressive tumor originating from neural stem cells of the central nervous system, which has high histopathological and genomic diversity. Mitochondria are cellular organelles associated with the regulation of cellular metabolism, redox signaling, energy generation, regulation of cell proliferation, and apoptosis. Accumulation of mutations in mitochondrial DNA (mtDNA) leads to mitochondrial dysfunction that plays an important role in GBM pathogenesis, favoring abnormal energy and reactive oxygen species production and resistance to apoptosis and to chemotherapeutic agents. The present review summarizes the known mitochondrial DNA alterations related to GBM, their cellular and metabolic consequences, and their association with diagnosis, prognosis, and treatment.

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High mitochondrial DNA copy number is associated with longer survival in young patients with glioblastoma

Cited by 10 publications

References 5 publications

High Tumor Mitochondrial DNA Content Correlates With an Improved Patient's Outcome in WHO Grade III Meningioma

High Tumor Mitochondrial DNA Content Correlates With an Improved Patient's Outcome in WHO Grade III Meningioma

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

Mitochondrial DNA Alterations in Glioblastoma (GBM)

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