title: A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most malignant brain cancer in adults, with a poor prognosis, whose molecular stratification still represents a challenge in pathology and clinics. On the other hand, mitochondrial DNA (mtDNA) mutations have been found in most tumors as modifiers of the bioenergetics state, albeit in GBM a characterization of the mtDNA status is lacking to date. Here, a characterization of the burden of mtDNA mutations in GBM samples was performed. First, investigation of tumor-specific vs. non tumor-specific mutations was carried out with the MToolBox bioinformatics pipeline by analyzing 45 matched tumor/blood samples, from whole genome or whole exome sequencing datasets obtained from The Cancer Genome Atlas (TCGA) consortium. Additionally, the entire mtDNA sequence was obtained in a dataset of 104 fresh-frozen GBM samples. Mitochondrial mutations with potential pathogenic interest were prioritized based on heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. A preliminary biochemical analysis of the activity of mitochondrial respiratory complexes was also performed on fresh-frozen GBM samples. Although a high number of mutations was detected, we report that the large majority of them does not pass the prioritization filters. Therefore, a relatively limited burden of pathogenic mutations is indeed carried by GBM, which did not appear to determine a general impairment of the respiratory chain. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors: Michele
authors: M
authors: Vidone
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors: Rosanna
authors: R
authors: Clima
authors: Department of Sciences and Technologies, University of Sannio, Benevento, Italy.
authors: Mariangela
authors: M
authors: Santorsola
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors: Claudia
authors: C
authors: Calabrese
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors: Giulia
authors: G
authors: Girolimetti
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors: Ivana
authors: I
authors: Kurelac
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors: Laura Benedetta
authors: LB
authors: Amato
authors: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors: Luisa
authors: L
authors: Iommarini
authors: Division of Neurology, Hospital of Rivoli, Rivoli, Italy.
authors: Elisa
authors: E
authors: Trevisan
authors: Department of Pathology OIRM-S. Anna Hospital, A.O.U. City of Health and Science, Turin, Italy.
authors: Marco
authors: M
authors: Leone
authors: Department of Neuro-Oncology, University and A.O.U. City of Health and Science, Turin, Italy.
authors: Riccardo
authors: R
authors: Soffietti
authors: Department of Pathology OIRM-S. Anna Hospital, A.O.U. City of Health and Science, Turin, Italy.
authors: Isabella
authors: I
authors: Morra
authors: Department of Neurosurgery CTO Hospital, A.O.U. City of Health and Science, Turin, Italy.
authors: Giuliano
authors: G
authors: Faccani
authors: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors: Marcella
authors: M
authors: Attimonelli
authors: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors: Anna Maria
authors: AM
authors: Porcelli
authors: Department of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University of Bologna, Bologna, Italy. Electronic address: giuseppe.gasparre@gmail.com.
authors: Giuseppe
authors: G
authors: Gasparre
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D059472:Exome / Q000235:genetics; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial
keywords: Glioblastoma multiforme; Mitochondrial DNA mutations; Warburg effect