A mechanistic classification of clinical phenotypes in neuroblastoma
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. seq...
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| Published in | Science (American Association for the Advancement of Science) Vol. 362; no. 6419; pp. 1165 - 1170 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
The American Association for the Advancement of Science
07.12.2018
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| Subjects | |
| Online Access | Get full text |
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| Abstract | 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.
1165
Neuroblastomas that are positive for telomere maintenance mechanisms are associated with a poorer prognosis.
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. |
|---|---|
| AbstractList | 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.
1165
Neuroblastomas that are positive for telomere maintenance mechanisms are associated with a poorer prognosis.
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. 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. A systematic look at a childhood tumorNeuroblastomas—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. 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.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. |
| Author | Gartlgruber, Moritz Schramm, Alexander Hero, Barbara Menon, Roopika Altmüller, Janine Singhi, Aatur D. Vokuhl, Christian Fischer, Janina Roderwieser, Andrea Gecht, Judith Speleman, Frank Okonechnikov, Konstantin Simon, Thorsten Schulte, Johannes H. Büttner, Reinhard Hertwig, Falk Vogel, Wenzel Fischer, Matthias Volland, Ruth Sand, Frederik Krug, Barbara Achter, Viktor Lang, Ulrich Welte, Anne Heuckmann, Johannes M. Theissen, Jessica Schmidt, Matthias Kahlert, Yvonne Hartlieb, Sabine Walter, Esther Ikram, Fakhera Westermann, Frank Thomas, Roman K. Eggert, Angelika Nürnberg, Peter Berthold, Frank Vandesompele, Jo Ortmann, Monika Perner, Sven Rosswog, Carolina O’Sullivan, Roderick J. de Wilde, Bram Bartenhagen, Christoph Kerschke, Laura Peifer, Martin Ackermann, Sandra Henrich, Kai-Oliver Lefever, Steve Cartolano, Maria Rahmann, Sven |
| AuthorAffiliation | 19 Department of Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany 14 German Cancer Consortium (DKTK), Heidelberg, Germany 15 Berlin Institute of Health, Berlin, Germany 17 Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany 29 Department of Medical Oncology, West German Cancer Center Essen, University of Duisburg-Essen, Essen, Germany 20 Department of Nuclear Medicine, University of Cologne, Cologne, Germany 8 Division of Pediatric Neurooncology, German Cancer Research Center, and Hopp Children's Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany 12 Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan 26 Department of Pathology, University of Cologne, Cologne, Germany 22 Computer Science, TU Dortmund, Dortmund, Germany 6 NEO New Oncology GmbH, Cologne, Germany 24 Department of Informatics, University of Cologne, Cologne, Germany 3 |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30523111$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work. Author contributions: Conception and design: S.A., M.P., and M.F. Administrative support and provision of study materials and patients: B.H., T.S., W.V., S.P., B.K., M.S., S.R., V.A., U.L., C.V., R.B., A.E., F.Sp., R.J.O., R.K.T., F.B., J.V., A.S., F.W., J.H.S., M.P., and M.F. Conduct of the experiments, data analysis, and interpretation: S.A., M.C., B.H., A.W., Y.K., A.R., C.B., E.W., J.G., L.K., R.V., R.M., J.M.H., M.G., S.H., K.O.H., K.O., J.A., P.N., S.L., B.D.W., F.Sa., F.I., C.R., J.F., J.T., F.H., A.D.S., M.O., F.Sp., R.J.O., R.K.T., F.B., J.V., A.S., F.W., J.H.S., M.P., and M.F. Manuscript writing: S.A., M.C., M.P., and M.F. All authors read and approved the final manuscript |
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| Snippet | Neuroblastomas—the most common tumor type in infants—develop from fetal nerve cells, and their clinical course is highly variable. Some neuroblastomas are... Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To... A systematic look at a childhood tumorNeuroblastomas—the most common tumor type in infants—develop from fetal nerve cells, and their clinical course is highly... |
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| SubjectTerms | Anatomy Child Child, Preschool Children Classification Disease-Free Survival Exome - genetics Fetuses Gene sequencing Genome, Human Genomes Genotype & phenotype Humans Infants Maintenance Medical prognosis Metabolic Networks and Pathways - genetics Mutation Neuroblastoma Neuroblastoma - classification Neuroblastoma - drug therapy Neuroblastoma - genetics Neuroblastoma - mortality p53 Protein Patients Phenotypes Pretreatment Prognosis ras Proteins - genetics Regression Risk Sequence Analysis, DNA Survival Sympathetic nervous system Telomere Homeostasis - genetics Tumor Suppressor Protein p53 - genetics Tumors Yeast |
| Title | A mechanistic classification of clinical phenotypes in neuroblastoma |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/30523111 https://www.proquest.com/docview/2153686128 https://www.proquest.com/docview/2155928913 https://pubmed.ncbi.nlm.nih.gov/PMC7875194 |
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