A mechanistic classification of clinical phenotypes in neuroblastoma

Sandra Ackermann; Maria Cartolano; Barbara Hero; Anne Welte; Yvonne Kahlert; Andrea Roderwieser; Christoph Bartenhagen; Esther Walter; Judith Gecht; Laura Kerschke; Ruth Volland; Roopika Menon; Johannes M. Heuckmann; Moritz Gartlgruber; Sabine Hartlieb; Kai Oliver Henrich; Konstantin Okonechnikov; Janine Altmüller; Peter Nürnberg; Steve Lefever; Bram De Wilde; Frederik Sand; Fakhera Ikram; Carolina Rosswog; Janina Fischer; Jessica Theissen; Falk Hertwig; Aatur D. Singhi; Thorsten Simon; Wenzel Vogel; Sven Perner; Barbara Krug; Matthias Schmidt; Sven Rahmann; Viktor Achter; Ulrich Lang; Christian Vokuhl; Monika Ortmann; Reinhard Büttner; Angelika Eggert; Frank Speleman; Roderick J. O’Sullivan; Roman K. Thomas; Frank Berthold; Jo Vandesompele; Alexander Schramm; Frank Westermann; Johannes H. Schulte; Martin Peifer; Matthias Fischer

doi:10.1126/science.aat6768

A mechanistic classification of clinical phenotypes in neuroblastoma

Sandra Ackermann, Maria Cartolano, Barbara Hero, Anne Welte, Yvonne Kahlert, Andrea Roderwieser, Christoph Bartenhagen, Esther Walter, Judith Gecht, Laura Kerschke, Ruth Volland, Roopika Menon, Johannes M. Heuckmann, Moritz Gartlgruber, Sabine Hartlieb, Kai Oliver Henrich, Konstantin Okonechnikov, Janine Altmüller, Peter Nürnberg, Steve LefeverBram De Wilde, Frederik Sand, Fakhera Ikram, Carolina Rosswog, Janina Fischer, Jessica Theissen, Falk Hertwig, Aatur D. Singhi, Thorsten Simon, Wenzel Vogel, Sven Perner, Barbara Krug, Matthias Schmidt, Sven Rahmann, Viktor Achter, Ulrich Lang, Christian Vokuhl, Monika Ortmann, Reinhard Büttner, Angelika Eggert, Frank Speleman, Roderick J. O’Sullivan, Roman K. Thomas, Frank Berthold, Jo Vandesompele, Alexander Schramm, Frank Westermann, Johannes H. Schulte, Martin Peifer, Matthias Fischer^*

^*Corresponding author for this work

Institute of Pathology

34 Citations (Scopus)

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.

Original language	English
Journal	Science
Volume	362
Issue number	6419
Pages (from-to)	1165-1170
Number of pages	6
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.aat6768
Publication status	Published - 07.12.2018

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Ackermann, S., Cartolano, M., Hero, B., Welte, A., Kahlert, Y., Roderwieser, A., Bartenhagen, C., Walter, E., Gecht, J., Kerschke, L., Volland, R., Menon, R., Heuckmann, J. M., Gartlgruber, M., Hartlieb, S., Henrich, K. O., Okonechnikov, K., Altmüller, J., Nürnberg, P., ... Fischer, M. (2018). A mechanistic classification of clinical phenotypes in neuroblastoma. Science, 362(6419), 1165-1170. https://doi.org/10.1126/science.aat6768

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title = "A mechanistic classification of clinical phenotypes in neuroblastoma",

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.",

author = "Sandra Ackermann and Maria Cartolano and Barbara Hero and Anne Welte and Yvonne Kahlert and Andrea Roderwieser and Christoph Bartenhagen and Esther Walter and Judith Gecht and Laura Kerschke and Ruth Volland and Roopika Menon and Heuckmann, {Johannes M.} and Moritz Gartlgruber and Sabine Hartlieb and Henrich, {Kai Oliver} and Konstantin Okonechnikov and Janine Altm{\"u}ller and Peter N{\"u}rnberg and Steve Lefever and {De Wilde}, Bram and Frederik Sand and Fakhera Ikram and Carolina Rosswog and Janina Fischer and Jessica Theissen and Falk Hertwig and Singhi, {Aatur D.} and Thorsten Simon and Wenzel Vogel and Sven Perner and Barbara Krug and Matthias Schmidt and Sven Rahmann and Viktor Achter and Ulrich Lang and Christian Vokuhl and Monika Ortmann and Reinhard B{\"u}ttner and Angelika Eggert and Frank Speleman and O{\textquoteright}Sullivan, {Roderick J.} and Thomas, {Roman K.} and Frank Berthold and Jo Vandesompele and Alexander Schramm and Frank Westermann and Schulte, {Johannes H.} and Martin Peifer and Matthias Fischer",

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Ackermann, S, Cartolano, M, Hero, B, Welte, A, Kahlert, Y, Roderwieser, A, Bartenhagen, C, Walter, E, Gecht, J, Kerschke, L, Volland, R, Menon, R, Heuckmann, JM, Gartlgruber, M, Hartlieb, S, Henrich, KO, Okonechnikov, K, Altmüller, J, Nürnberg, P, Lefever, S, De Wilde, B, Sand, F, Ikram, F, Rosswog, C, Fischer, J, Theissen, J, Hertwig, F, Singhi, AD, Simon, T, Vogel, W, Perner, S, Krug, B, Schmidt, M, Rahmann, S, Achter, V, Lang, U, Vokuhl, C, Ortmann, M, Büttner, R, Eggert, A, Speleman, F, O’Sullivan, RJ, Thomas, RK, Berthold, F, Vandesompele, J, Schramm, A, Westermann, F, Schulte, JH, Peifer, M & Fischer, M 2018, 'A mechanistic classification of clinical phenotypes in neuroblastoma', Science, vol. 362, no. 6419, pp. 1165-1170. https://doi.org/10.1126/science.aat6768

TY - JOUR

T1 - A mechanistic classification of clinical phenotypes in neuroblastoma

AU - Ackermann, Sandra

AU - Cartolano, Maria

AU - Hero, Barbara

AU - Welte, Anne

AU - Kahlert, Yvonne

AU - Roderwieser, Andrea

AU - Bartenhagen, Christoph

AU - Walter, Esther

AU - Gecht, Judith

AU - Kerschke, Laura

AU - Volland, Ruth

AU - Menon, Roopika

AU - Heuckmann, Johannes M.

AU - Gartlgruber, Moritz

AU - Hartlieb, Sabine

AU - Henrich, Kai Oliver

AU - Okonechnikov, Konstantin

AU - Altmüller, Janine

AU - Nürnberg, Peter

AU - Lefever, Steve

AU - De Wilde, Bram

AU - Sand, Frederik

AU - Ikram, Fakhera

AU - Rosswog, Carolina

AU - Fischer, Janina

AU - Theissen, Jessica

AU - Hertwig, Falk

AU - Singhi, Aatur D.

AU - Simon, Thorsten

AU - Vogel, Wenzel

AU - Perner, Sven

AU - Krug, Barbara

AU - Schmidt, Matthias

AU - Rahmann, Sven

AU - Achter, Viktor

AU - Lang, Ulrich

AU - Vokuhl, Christian

AU - Ortmann, Monika

AU - Büttner, Reinhard

AU - Eggert, Angelika

AU - Speleman, Frank

AU - O’Sullivan, Roderick J.

AU - Thomas, Roman K.

AU - Berthold, Frank

AU - Vandesompele, Jo

AU - Schramm, Alexander

AU - Westermann, Frank

AU - Schulte, Johannes H.

AU - Peifer, Martin

AU - Fischer, Matthias

PY - 2018/12/7

Y1 - 2018/12/7

N2 - 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.

AB - 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.

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U2 - 10.1126/science.aat6768

DO - 10.1126/science.aat6768

M3 - Journal articles

C2 - 30523111

AN - SCOPUS:85057763642

SN - 0036-8075

VL - 362

SP - 1165

EP - 1170

JO - Science

JF - Science

IS - 6419

ER -

A mechanistic classification of clinical phenotypes in neuroblastoma

Abstract

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