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A mechanistic classification of clinical phenotypes in neuroblastoma

Item Type:Article
Title:A mechanistic classification of clinical phenotypes in neuroblastoma
Creators Name:Ackermann, S. and Cartolano, M. and Hero, B. and Welte, A. and Kahlert, Y. and Roderwieser, A. and Bartenhagen, C. and Walter, E. and Gecht, J. and Kerschke, L. and Volland, R. and Menon, R. and Heuckmann, J.M. and Gartlgruber, M. and Hartlieb, S. and Henrich, K.O. and Okonechnikov, K. and Altmüller, J. and Nürnberg, P. and Lefever, S. and de Wilde, B. and Sand, F. and Ikram, F. and Rosswog, C. and Fischer, J. and Theissen, J. and Hertwig, F. and Singhi, A.D. and Simon, T. and Vogel, W. and Perner, S. and Krug, B. and Schmidt, M. and Rahmann, S. and Achter, V. and Lang, U. and Vokuhl, C. and Ortmann, M. and Büttner, R. and Eggert, A. and Speleman, F. and O'Sullivan, R.J. and Thomas, R.K. and Berthold, F. and Vandesompele, J. and Schramm, A. and Westermann, F. and Schulte, J.H. and Peifer, M. and Fischer, M.
Abstract:Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance-negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.
Keywords:DNA Sequence Analysis, Disease-Free Survival, Exome, Human Genome, Metabolic Networks and Pathways, Mutation, Neuroblastoma, Prognosis, ras Proteins, Telomere Homeostasis, Tumor Suppressor Protein p53
Publisher:American Association for the Advancement of Science
Page Range:1165-1170
Date:7 December 2018
Official Publication:https://doi.org/10.1126/science.aat6768
PubMed:View item in PubMed

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