The landscape of genomic alterations across childhood cancers
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The landscape of genomic alterations across childhood cancers. / Gröbner, Susanne N; Worst, Barbara C; Weischenfeldt, Joachim; Buchhalter, Ivo; Kleinheinz, Kortine; Rudneva, Vasilisa A; Johann, Pascal D; Balasubramanian, Gnana Prakash; Segura-Wang, Maia; Brabetz, Sebastian; Bender, Sebastian; Hutter, Barbara; Sturm, Dominik; Pfaff, Elke; Hübschmann, Daniel; Zipprich, Gideon; Heinold, Michael; Eils, Jürgen; Lawerenz, Christian; Erkek, Serap; Lambo, Sander; Waszak, Sebastian; Blattmann, Claudia; Borkhardt, Arndt; Kuhlen, Michaela; Eggert, Angelika; Fulda, Simone; Gessler, Manfred; Wegert, Jenny; Kappler, Roland; Baumhoer, Daniel; Burdach, Stefan; Kirschner-Schwabe, Renate; Kontny, Udo; Kulozik, Andreas E; Lohmann, Dietmar; Hettmer, Simone; Eckert, Cornelia; Bielack, Stefan; Nathrath, Michaela; Niemeyer, Charlotte; Richter, Günther H; Schulte, Johannes; Siebert, Reiner; Westermann, Frank; Molenaar, Jan J; Vassal, Gilles; Witt, Hendrik; Burkhardt, Birgit; Kratz, Christian P; Witt, Olaf; van Tilburg, Cornelis M; Kramm, Christof M; Fleischhack, Gudrun; Dirksen, Uta; Rutkowski, Stefan; Frühwald, Michael; von Hoff, Katja; Wolf, Stephan; Klingebiel, Thomas; Koscielniak, Ewa; Landgraf, Pablo; Koster, Jan; Resnick, Adam C; Zhang, Jinghui; Liu, Yanling; Zhou, Xin; Waanders, Angela J; Zwijnenburg, Danny A; Raman, Pichai; Brors, Benedikt; Weber, Ursula D; Northcott, Paul A; Pajtler, Kristian W; Kool, Marcel; Piro, Rosario M; Korbel, Jan O; Schlesner, Matthias; Eils, Roland; Jones, David T W; Lichter, Peter; Chavez, Lukas; Zapatka, Marc; Pfister, Stefan M; ICGC PedBrain-Seq Project.
In: NATURE, Vol. 555, No. 7696, 15.03.2018, p. 321-327.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The landscape of genomic alterations across childhood cancers
AU - Gröbner, Susanne N
AU - Worst, Barbara C
AU - Weischenfeldt, Joachim
AU - Buchhalter, Ivo
AU - Kleinheinz, Kortine
AU - Rudneva, Vasilisa A
AU - Johann, Pascal D
AU - Balasubramanian, Gnana Prakash
AU - Segura-Wang, Maia
AU - Brabetz, Sebastian
AU - Bender, Sebastian
AU - Hutter, Barbara
AU - Sturm, Dominik
AU - Pfaff, Elke
AU - Hübschmann, Daniel
AU - Zipprich, Gideon
AU - Heinold, Michael
AU - Eils, Jürgen
AU - Lawerenz, Christian
AU - Erkek, Serap
AU - Lambo, Sander
AU - Waszak, Sebastian
AU - Blattmann, Claudia
AU - Borkhardt, Arndt
AU - Kuhlen, Michaela
AU - Eggert, Angelika
AU - Fulda, Simone
AU - Gessler, Manfred
AU - Wegert, Jenny
AU - Kappler, Roland
AU - Baumhoer, Daniel
AU - Burdach, Stefan
AU - Kirschner-Schwabe, Renate
AU - Kontny, Udo
AU - Kulozik, Andreas E
AU - Lohmann, Dietmar
AU - Hettmer, Simone
AU - Eckert, Cornelia
AU - Bielack, Stefan
AU - Nathrath, Michaela
AU - Niemeyer, Charlotte
AU - Richter, Günther H
AU - Schulte, Johannes
AU - Siebert, Reiner
AU - Westermann, Frank
AU - Molenaar, Jan J
AU - Vassal, Gilles
AU - Witt, Hendrik
AU - Burkhardt, Birgit
AU - Kratz, Christian P
AU - Witt, Olaf
AU - van Tilburg, Cornelis M
AU - Kramm, Christof M
AU - Fleischhack, Gudrun
AU - Dirksen, Uta
AU - Rutkowski, Stefan
AU - Frühwald, Michael
AU - von Hoff, Katja
AU - Wolf, Stephan
AU - Klingebiel, Thomas
AU - Koscielniak, Ewa
AU - Landgraf, Pablo
AU - Koster, Jan
AU - Resnick, Adam C
AU - Zhang, Jinghui
AU - Liu, Yanling
AU - Zhou, Xin
AU - Waanders, Angela J
AU - Zwijnenburg, Danny A
AU - Raman, Pichai
AU - Brors, Benedikt
AU - Weber, Ursula D
AU - Northcott, Paul A
AU - Pajtler, Kristian W
AU - Kool, Marcel
AU - Piro, Rosario M
AU - Korbel, Jan O
AU - Schlesner, Matthias
AU - Eils, Roland
AU - Jones, David T W
AU - Lichter, Peter
AU - Chavez, Lukas
AU - Zapatka, Marc
AU - Pfister, Stefan M
AU - ICGC PedBrain-Seq Project
PY - 2018/3/15
Y1 - 2018/3/15
N2 - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
AB - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/nature25480
DO - 10.1038/nature25480
M3 - SCORING: Journal article
C2 - 29489754
VL - 555
SP - 321
EP - 327
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 7696
ER -