The mitochondrial genetic landscape in neuroblastoma from tumor initiation to relapse.

// Lara M. Riehl 1 , Johannes H. Schulte 2, 3 , Medhanie A. Mulaw 4, 5 , Meike Dahlhaus 1 , Matthias Fischer 6, 7 , Alexander Schramm 8 , Angelika Eggert 2 , Klaus-Michael Debatin 1 , Christian Beltinger 1 1 Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany 2 Pediatric Oncology and Hematology, Charite University Medicine, Berlin, Germany 3 German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany 4 Institute for Experimental Cancer Research, University Medical Center Ulm, Ulm, Germany 5 Core Facility Genomics, Faculty of Medicine, Ulm University, Ulm, Germany 6 Department of Pediatric Oncology and Hematology, University Children’s Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany 7 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany 8 Department of Pediatric Oncology and Hematology, University Children’s Hospital Essen, Essen, Germany Correspondence to: Christian Beltinger, e-mail: christian.beltinger@uniklinik-ulm.de Keywords: mitochondrial variants, neuroblastoma, tumor progression, next generation sequencing, phylogenetic analysis Received: September 01, 2015      Accepted: November 25, 2015      Published: December 28, 2015 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.