title: The mitochondrial genetic landscape in neuroblastoma from tumor initiation to relapse.
abstract: Little is known about changes within the mitochondrial (mt) genome during tumor progression in general and during initiation and progression of neuroblastoma (NB) in particular. Whole exome sequencing of corresponding healthy tissue, primary tumor and relapsed tumor from 16 patients with NB revealed that most NB harbor tumor-specific mitochondrial variants. In relapsed tumors, the status of mt variants changed in parallel to the status of nuclear variants, as shown by increased number and spatio-temporal differences of tumor-specific variants, and by a concomitant decrease of germline variants. As mt variants are present in most NB patients, change during relapse and have a higher copy number compared to nuclear variants, they represent a promising new source of biomarkers for monitoring and phylogenetic analysis of NB.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Lara M
authors.initials: LM
authors.lastname: Riehl
authors.affiliation: Pediatric Oncology and Hematology, Charité University Medicine, Berlin, Germany.|German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.affiliation: Institute for Experimental Cancer Research, University Medical Center Ulm, Ulm, Germany.|Core Facility Genomics, Faculty of Medicine, Ulm University, Ulm, Germany.
authors.forename: Medhanie A
authors.initials: MA
authors.lastname: Mulaw
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Dahlhaus
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.affiliation: Pediatric Oncology and Hematology, Charité University Medicine, Berlin, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beltinger
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018450:Disease Progression; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D024101:Mitochondrial Proteins
keywords: mitochondrial variants; neuroblastoma; next generation sequencing; phylogenetic analysis; tumor progression