title: A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma.
abstract: BACKGROUND
  Neuroblastoma, a tumor of the developing sympathetic nervous system, is a common childhood neoplasm that is often lethal. Mitochondrial DNA (mtDNA) mutations have been found in most tumors including neuroblastoma. We extracted mtDNA data from a cohort of neuroblastoma samples that had undergone Whole Exome Sequencing (WES) and also used snap-frozen samples in which mtDNA was entirely sequenced by Sanger technology. We next undertook the challenge of determining those mutations that are relevant to, or arisen during tumor development. The bioinformatics pipeline used to extract mitochondrial variants from matched tumor/blood samples was enriched by a set of filters inclusive of heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity.
  
  
  RESULTS
  Our in silico multistep workflow applied both on WES and Sanger-sequenced neuroblastoma samples, allowed us to identify a limited burden of somatic and germline mitochondrial mutations with a potential pathogenic impact.
  
  
  CONCLUSIONS
  The few singleton germline and somatic mitochondrial mutations emerged, according to our in silico analysis, do not appear to impact on the development of neuroblastoma. Our findings are consistent with the hypothesis that most mitochondrial somatic mutations can be considered as 'passengers' and consequently have no discernible effect in this type of cancer.
authors.affiliation: Department of Biology, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Francesco Maria
authors.initials: FM
authors.lastname: Calabrese
authors.affiliation: Department of Medical and Surgical Sciences-DIMEC, Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Clima
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Pignataro
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Vito Alessandro
authors.initials: VA
authors.lastname: Lasorsa
authors.affiliation: Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hogarty
authors.affiliation: Paediatric Haematology/Oncology Department, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Castellano
authors.affiliation: Oncology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.affiliation: Pediatric Research Institute (IRP) - Fondazione Città della Speranza, Neuroblastoma Laboratory, Padua, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.affiliation: Department of Medical and Surgical Sciences-DIMEC, Medical Genetics Unit, University of Bologna, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gasparre
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.|IRCCS SDN, Istituto di Ricerca Diagnostica e Nucleare, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Capasso
mesh_terms: D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D004252:DNA Mutational Analysis / Q000379:methods*; D004272:DNA, Mitochondrial / Q000235:genetics*; D059472:Exome; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype
chemical_list: D004272:DNA, Mitochondrial
keywords: WES; germline mutations; mitochondrial DNA mutations; neuroblastoma; somatic mutations