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The landscape of genomic alterations across childhood cancers
Susanne N. Gröbner ,
Barbara C. Worst ,
Joachim Weischenfeldt ,
Ivo Buchhalter ,
Kortine Kleinheinz ,
Vasilisa A. Rudneva ,
Pascal D. Johann ,
Gnana Prakash Balasubramanian ,
Maia Segura-Wang ,
Sebastian Brabetz ,
Sebastian Bender ,
Barbara Hutter ,
Dominik Sturm ,
Elke Pfaff ,
Daniel Hübschmann ,
Gideon Zipprich ,
Michael Heinold ,
Jürgen Eils ,
Christian Lawerenz ,
Serap Erkek ,
Sander Lambo ,
Sebastian Waszak ,
Claudia Blattmann ,
Arndt Borkhardt ,
Michaela Kuhlen ,
Angelika Eggert ,
Simone Fulda ,
Manfred Gessler ,
Jenny Wegert ,
Roland Kappler ,
Daniel Baumhoer ,
Stefan Burdach ,
Renate Kirschner-Schwabe ,
Udo Kontny ,
Andreas E. Kulozik ,
Dietmar Lohmann ,
Simone Hettmer ,
Cornelia Eckert ,
Stefan Bielack ,
Michaela Nathrath ,
Charlotte Niemeyer ,
Günther H. Richter ,
Johannes Schulte ,
Reiner Siebert ,
Frank Westermann ,
Jan J. Molenaar ,
Gilles Vassal ,
Hendrik Witt ,
Peter Lichter ,
Ursula Weber ,
Roland Eils ,
Andrey Korshunov ,
Olaf Witt ,
Stefan Pfister ,
Guido Reifenberger ,
Jörg Felsberg ,
Christof von Kalle ,
Manfred Schmidt ,
Cynthia Bartholomä ,
Michael Taylor ,
Stefan Pfister ,
David Jones ,
Peter Lichter ,
Natalie Jäger ,
Ivo Buchhalter ,
Jan Korbel ,
Adrian Stütz ,
Tobias Rausch ,
Bernhard Radlwimmer ,
Marie-Laure Yaspo ,
Hans Lehrach ,
Hans-Jörg Warnatz ,
Pablo Landgraf ,
Arndt Borkhardt ,
Benedikt Brors ,
Marc Zapatka ,
Roland Eils ,
Roland Eils ,
Jürgen Eils ,
Christian Lawerenz ,
Reiner Siebert ,
Susanne Wagner ,
Andrea Haake ,
Julia Richter ,
Gesine Richter ,
Roland Eils ,
Chris Lawerenz ,
Jürgen Eils ,
Jules Kerssemakers ,
Christina Jaeger-Schmidt ,
Ingrid Scholz ,
Anke K. Bergmann ,
Christoph Borst ,
Birgit Burkhardt ,
Alexander Claviez ,
Martin Dreyling ,
Sonja Eberth ,
Hermann Einsele ,
Norbert Frickhofen ,
Siegfried Haas ,
Martin-Leo Hansmann ,
Dennis Karsch ,
Michael Kneba ,
Jasmin Lisfeld ,
Luisa Mantovani-Löffler ,
Marius Rohde ,
German Ott ,
Christina Stadler ,
Peter Staib ,
Stephan Stilgenbauer ,
Lorenz Trümper ,
Thorsten Zenz ,
Martin-Leo Hansmann ,
Dieter Kube ,
Ralf Küppers ,
Marc Weniger ,
Michael Hummel ,
Wolfram Klapper ,
Ulrike Kostezka ,
Dido Lenze ,
Peter Möller ,
Andreas Rosenwald ,
German Ott ,
Monika Szczepanowski ,
Ole Ammerpohl ,
Sietse M. Aukema ,
Vera Binder ,
Arndt Borkhardt ,
Andrea Haake ,
Jessica I. Hoell ,
Ellen Leich ,
Peter Lichter ,
Cristina López ,
Inga Nagel ,
Jordan Pischimariov ,
Bernhard Radlwimmer ,
Julia Richter ,
Philip Rosenstiel ,
Andreas Rosenwald ,
Markus Schilhabel ,
Stefan Schreiber ,
Inga Vater ,
Rabea Wagener ,
Reiner Siebert ,
Stephan H. Bernhart ,
Hans Binder ,
Benedikt Brors ,
Gero Doose ,
Roland Eils ,
Steve Hoffmann ,
Lydia Hopp ,
Daniel Hübschmann ,
Kortine Kleinheinz ,
Helene Kretzmer ,
Markus Kreuz ,
Jan Korbel ,
David Langenberger ,
Markus Loeffler ,
Maciej Rosolowski ,
Matthias Schlesner ,
Peter F. Stadler ,
Stephanie Sungalee ,
Birgit Burkhardt ,
Christian P. Kratz ,
Olaf Witt ,
Cornelis M. van Tilburg ,
Christof M. Kramm ,
Gudrun Fleischhack ,
Uta Dirksen ,
Stefan Rutkowski ,
Michael Frühwald ,
Katja von Hoff ,
Stephan Wolf ,
Thomas Klingebiel ,
Ewa Koscielniak ,
Pablo Landgraf ,
Jan Koster ,
Adam C. Resnick ,
Jinghui Zhang ,
Yanling Liu ,
Xin Zhou ,
Angela J. Waanders ,
Danny A. Zwijnenburg ,
Pichai Raman ,
Benedikt Brors ,
Ursula D. Weber ,
Paul A. Northcott ,
Kristian W. Pajtler ,
Marcel Kool ,
Rosario M. Piro ,
Jan O. Korbel ,
Matthias Schlesner ,
Roland Eils ,
David T. W. Jones ,
Peter Lichter ,
Lukas Chavez ,
Marc Zapatka ,
Stefan M. Pfister
February 28 2018
February 28 2018
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Abstract
<p class="first" id="d3284689e1256">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.
</p>