A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma

Francesco Maria Calabrese, Rosanna Clima, Piero Pignataro, Vito Alessandro Lasorsa, Michael D. Hogarty, Aurora Castellano, Massimo Conte, Gian Paolo Tonini, Achille Iolascon, Giuseppe Gasparre, Mario Capasso

Research output: Contribution to journalArticlepeer-review


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 Sangersequenced 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.

Original languageEnglish
Pages (from-to)49246-49258
Number of pages13
Issue number31
Publication statusPublished - 2016


  • Germline mutations
  • Mitochondrial DNA mutations
  • Neuroblastoma
  • Somatic mutations
  • WES

ASJC Scopus subject areas

  • Oncology


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