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The whole-genome landscape of medulloblastoma subtypes. / Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A.; Warnatz, Hans Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T.W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M.G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J.M.; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter.
In:
Nature, Vol. 547, No. 7663, 19.07.2017, p. 311-317.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Northcott, PA, Buchhalter, I, Morrissy, AS, Hovestadt, V
, Weischenfeldt, J, Ehrenberger, T, Gröbner, S, Segura-Wang, M, Zichner, T, Rudneva, VA, Warnatz, HJ, Sidiropoulos, N, Phillips, AH, Schumacher, S, Kleinheinz, K, Waszak, SM, Erkek, S, Jones, DTW, Worst, BC, Kool, M, Zapatka, M, Jäger, N, Chavez, L, Hutter, B, Bieg, M, Paramasivam, N, Heinold, M, Gu, Z, Ishaque, N, Jäger-Schmidt, C, Imbusch, CD, Jugold, A, Hübschmann, D, Risch, T, Amstislavskiy, V, Gonzalez, FGR, Weber, UD, Wolf, S, Robinson, GW, Zhou, X, Wu, G, Finkelstein, D, Liu, Y, Cavalli, FMG, Luu, B, Ramaswamy, V, Wu, X, Koster, J, Ryzhova, M, Cho, YJ, Pomeroy, SL, Herold-Mende, C, Schuhmann, M, Ebinger, M, Liau, LM, Mora, J, McLendon, RE, Jabado, N, Kumabe, T, Chuah, E, Ma, Y, Moore, RA, Mungall, AJ, Mungall, KL, Thiessen, N, Tse, K, Wong, T, Jones, SJM, Witt, O, Milde, T, Von Deimling, A, Capper, D, Korshunov, A, Yaspo, ML, Kriwacki, R, Gajjar, A, Zhang, J, Beroukhim, R, Fraenkel, E, Korbel, JO, Brors, B, Schlesner, M, Eils, R, Marra, MA, Pfister, SM, Taylor, MD & Lichter, P 2017, '
The whole-genome landscape of medulloblastoma subtypes',
Nature, vol. 547, no. 7663, pp. 311-317.
https://doi.org/10.1038/nature22973APA
Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V.
, Weischenfeldt, J., Ehrenberger, T., Gröbner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., Warnatz, H. J., Sidiropoulos, N., Phillips, A. H., Schumacher, S., Kleinheinz, K., Waszak, S. M., Erkek, S., Jones, D. T. W., Worst, B. C., ... Lichter, P. (2017).
The whole-genome landscape of medulloblastoma subtypes.
Nature,
547(7663), 311-317.
https://doi.org/10.1038/nature22973Vancouver
Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V
, Weischenfeldt J, Ehrenberger T et al.
The whole-genome landscape of medulloblastoma subtypes.
Nature. 2017 Jul 19;547(7663):311-317.
https://doi.org/10.1038/nature22973Author
Northcott, Paul A. ; Buchhalter, Ivo ; Morrissy, A. Sorana ; Hovestadt, Volker ; Weischenfeldt, Joachim ; Ehrenberger, Tobias ; Gröbner, Susanne ; Segura-Wang, Maia ; Zichner, Thomas ; Rudneva, Vasilisa A. ; Warnatz, Hans Jörg ; Sidiropoulos, Nikos ; Phillips, Aaron H. ; Schumacher, Steven ; Kleinheinz, Kortine ; Waszak, Sebastian M. ; Erkek, Serap ; Jones, David T.W. ; Worst, Barbara C. ; Kool, Marcel ; Zapatka, Marc ; Jäger, Natalie ; Chavez, Lukas ; Hutter, Barbara ; Bieg, Matthias ; Paramasivam, Nagarajan ; Heinold, Michael ; Gu, Zuguang ; Ishaque, Naveed ; Jäger-Schmidt, Christina ; Imbusch, Charles D. ; Jugold, Alke ; Hübschmann, Daniel ; Risch, Thomas ; Amstislavskiy, Vyacheslav ; Gonzalez, Francisco German Rodriguez ; Weber, Ursula D. ; Wolf, Stephan ; Robinson, Giles W. ; Zhou, Xin ; Wu, Gang ; Finkelstein, David ; Liu, Yanling ; Cavalli, Florence M.G. ; Luu, Betty ; Ramaswamy, Vijay ; Wu, Xiaochong ; Koster, Jan ; Ryzhova, Marina ; Cho, Yoon Jae ; Pomeroy, Scott L. ; Herold-Mende, Christel ; Schuhmann, Martin ; Ebinger, Martin ; Liau, Linda M. ; Mora, Jaume ; McLendon, Roger E. ; Jabado, Nada ; Kumabe, Toshihiro ; Chuah, Eric ; Ma, Yussanne ; Moore, Richard A. ; Mungall, Andrew J. ; Mungall, Karen L. ; Thiessen, Nina ; Tse, Kane ; Wong, Tina ; Jones, Steven J.M. ; Witt, Olaf ; Milde, Till ; Von Deimling, Andreas ; Capper, David ; Korshunov, Andrey ; Yaspo, Marie Laure ; Kriwacki, Richard ; Gajjar, Amar ; Zhang, Jinghui ; Beroukhim, Rameen ; Fraenkel, Ernest ; Korbel, Jan O. ; Brors, Benedikt ; Schlesner, Matthias ; Eils, Roland ; Marra, Marco A. ; Pfister, Stefan M. ; Taylor, Michael D. ; Lichter, Peter. / The whole-genome landscape of medulloblastoma subtypes. In: Nature. 2017 ; Vol. 547, No. 7663. pp. 311-317.
Bibtex
@article{4745c9303c7c47e9a29aa5c580576bfe,
title = "The whole-genome landscape of medulloblastoma subtypes",
abstract = "Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.",
author = "Northcott, {Paul A.} and Ivo Buchhalter and Morrissy, {A. Sorana} and Volker Hovestadt and Joachim Weischenfeldt and Tobias Ehrenberger and Susanne Gr{\"o}bner and Maia Segura-Wang and Thomas Zichner and Rudneva, {Vasilisa A.} and Warnatz, {Hans J{\"o}rg} and Nikos Sidiropoulos and Phillips, {Aaron H.} and Steven Schumacher and Kortine Kleinheinz and Waszak, {Sebastian M.} and Serap Erkek and Jones, {David T.W.} and Worst, {Barbara C.} and Marcel Kool and Marc Zapatka and Natalie J{\"a}ger and Lukas Chavez and Barbara Hutter and Matthias Bieg and Nagarajan Paramasivam and Michael Heinold and Zuguang Gu and Naveed Ishaque and Christina J{\"a}ger-Schmidt and Imbusch, {Charles D.} and Alke Jugold and Daniel H{\"u}bschmann and Thomas Risch and Vyacheslav Amstislavskiy and Gonzalez, {Francisco German Rodriguez} and Weber, {Ursula D.} and Stephan Wolf and Robinson, {Giles W.} and Xin Zhou and Gang Wu and David Finkelstein and Yanling Liu and Cavalli, {Florence M.G.} and Betty Luu and Vijay Ramaswamy and Xiaochong Wu and Jan Koster and Marina Ryzhova and Cho, {Yoon Jae} and Pomeroy, {Scott L.} and Christel Herold-Mende and Martin Schuhmann and Martin Ebinger and Liau, {Linda M.} and Jaume Mora and McLendon, {Roger E.} and Nada Jabado and Toshihiro Kumabe and Eric Chuah and Yussanne Ma and Moore, {Richard A.} and Mungall, {Andrew J.} and Mungall, {Karen L.} and Nina Thiessen and Kane Tse and Tina Wong and Jones, {Steven J.M.} and Olaf Witt and Till Milde and {Von Deimling}, Andreas and David Capper and Andrey Korshunov and Yaspo, {Marie Laure} and Richard Kriwacki and Amar Gajjar and Jinghui Zhang and Rameen Beroukhim and Ernest Fraenkel and Korbel, {Jan O.} and Benedikt Brors and Matthias Schlesner and Roland Eils and Marra, {Marco A.} and Pfister, {Stefan M.} and Taylor, {Michael D.} and Peter Lichter",
year = "2017",
month = jul,
day = "19",
doi = "10.1038/nature22973",
language = "English",
volume = "547",
pages = "311--317",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7663",
}
RIS
TY - JOUR
T1 - The whole-genome landscape of medulloblastoma subtypes
AU - Northcott, Paul A.
AU - Buchhalter, Ivo
AU - Morrissy, A. Sorana
AU - Hovestadt, Volker
AU - Weischenfeldt, Joachim
AU - Ehrenberger, Tobias
AU - Gröbner, Susanne
AU - Segura-Wang, Maia
AU - Zichner, Thomas
AU - Rudneva, Vasilisa A.
AU - Warnatz, Hans Jörg
AU - Sidiropoulos, Nikos
AU - Phillips, Aaron H.
AU - Schumacher, Steven
AU - Kleinheinz, Kortine
AU - Waszak, Sebastian M.
AU - Erkek, Serap
AU - Jones, David T.W.
AU - Worst, Barbara C.
AU - Kool, Marcel
AU - Zapatka, Marc
AU - Jäger, Natalie
AU - Chavez, Lukas
AU - Hutter, Barbara
AU - Bieg, Matthias
AU - Paramasivam, Nagarajan
AU - Heinold, Michael
AU - Gu, Zuguang
AU - Ishaque, Naveed
AU - Jäger-Schmidt, Christina
AU - Imbusch, Charles D.
AU - Jugold, Alke
AU - Hübschmann, Daniel
AU - Risch, Thomas
AU - Amstislavskiy, Vyacheslav
AU - Gonzalez, Francisco German Rodriguez
AU - Weber, Ursula D.
AU - Wolf, Stephan
AU - Robinson, Giles W.
AU - Zhou, Xin
AU - Wu, Gang
AU - Finkelstein, David
AU - Liu, Yanling
AU - Cavalli, Florence M.G.
AU - Luu, Betty
AU - Ramaswamy, Vijay
AU - Wu, Xiaochong
AU - Koster, Jan
AU - Ryzhova, Marina
AU - Cho, Yoon Jae
AU - Pomeroy, Scott L.
AU - Herold-Mende, Christel
AU - Schuhmann, Martin
AU - Ebinger, Martin
AU - Liau, Linda M.
AU - Mora, Jaume
AU - McLendon, Roger E.
AU - Jabado, Nada
AU - Kumabe, Toshihiro
AU - Chuah, Eric
AU - Ma, Yussanne
AU - Moore, Richard A.
AU - Mungall, Andrew J.
AU - Mungall, Karen L.
AU - Thiessen, Nina
AU - Tse, Kane
AU - Wong, Tina
AU - Jones, Steven J.M.
AU - Witt, Olaf
AU - Milde, Till
AU - Von Deimling, Andreas
AU - Capper, David
AU - Korshunov, Andrey
AU - Yaspo, Marie Laure
AU - Kriwacki, Richard
AU - Gajjar, Amar
AU - Zhang, Jinghui
AU - Beroukhim, Rameen
AU - Fraenkel, Ernest
AU - Korbel, Jan O.
AU - Brors, Benedikt
AU - Schlesner, Matthias
AU - Eils, Roland
AU - Marra, Marco A.
AU - Pfister, Stefan M.
AU - Taylor, Michael D.
AU - Lichter, Peter
PY - 2017/7/19
Y1 - 2017/7/19
N2 - Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
AB - Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
U2 - 10.1038/nature22973
DO - 10.1038/nature22973
M3 - Journal article
C2 - 28726821
AN - SCOPUS:85025159196
VL - 547
SP - 311
EP - 317
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7663
ER -
