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.