RT Journal Article SR Electronic T1 A mechanistic classification of clinical phenotypes in neuroblastoma JF Science JO Science FD American Association for the Advancement of Science SP 1165 OP 1170 DO 10.1126/science.aat6768 VO 362 IS 6419 A1 Ackermann, Sandra A1 Cartolano, Maria A1 Hero, Barbara A1 Welte, Anne A1 Kahlert, Yvonne A1 Roderwieser, Andrea A1 Bartenhagen, Christoph A1 Walter, Esther A1 Gecht, Judith A1 Kerschke, Laura A1 Volland, Ruth A1 Menon, Roopika A1 Heuckmann, Johannes M. A1 Gartlgruber, Moritz A1 Hartlieb, Sabine A1 Henrich, Kai-Oliver A1 Okonechnikov, Konstantin A1 Altmüller, Janine A1 Nürnberg, Peter A1 Lefever, Steve A1 de Wilde, Bram A1 Sand, Frederik A1 Ikram, Fakhera A1 Rosswog, Carolina A1 Fischer, Janina A1 Theissen, Jessica A1 Hertwig, Falk A1 Singhi, Aatur D. A1 Simon, Thorsten A1 Vogel, Wenzel A1 Perner, Sven A1 Krug, Barbara A1 Schmidt, Matthias A1 Rahmann, Sven A1 Achter, Viktor A1 Lang, Ulrich A1 Vokuhl, Christian A1 Ortmann, Monika A1 Büttner, Reinhard A1 Eggert, Angelika A1 Speleman, Frank A1 O’Sullivan, Roderick J. A1 Thomas, Roman K. A1 Berthold, Frank A1 Vandesompele, Jo A1 Schramm, Alexander A1 Westermann, Frank A1 Schulte, Johannes H. A1 Peifer, Martin A1 Fischer, Matthias YR 2018 UL http://science.sciencemag.org/content/362/6419/1165.abstract AB Neuroblastomas—the most common tumor type in infants—develop from fetal nerve cells, and their clinical course is highly variable. Some neuroblastomas are fatal despite treatment, whereas others respond well to treatment and some undergo spontaneous regression without treatment. Ackermann et al. sequenced more than 400 pretreatment neuroblastomas and identified molecular features that characterize the three distinct clinical outcomes. Low-risk tumors lack telomere maintenance mechanisms, intermediate-risk tumors harbor telomere maintenance mechanisms, and high-risk tumors harbor telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations.Science, this issue p. 1165Neuroblastoma 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.