The landscape of genomic alterations across childhood cancers
Creators: name: Gröbner, Susanne N.
name: Worst, Barbara C.
name: Weischenfeldt, Joachim
name: Buchhalter, Ivo
name: Kleinheinz, Kortine
name: Rudneva, Vasilisa A.
name: Johann, Pascal D.
name: Balasubramanian, Gnana Prakash
name: Segura-Wang, Maia
name: Brabetz, Sebastian
name: Bender, Sebastian
name: Hutter, Barbara
name: Sturm, Dominik
name: Pfaff, Elke
name: Hübschmann, Daniel
name: Zipprich, Gideon
name: Heinold, Michael
name: Eils, Jürgen
name: Lawerenz, Christian
name: Erkek, Serap
name: Lambo, Sander
name: Waszak, Sebastian
name: Blattmann, Claudia
name: Borkhardt, Arndt
name: Kuhlen, Michaela
name: Eggert, Angelika
name: Fulda, Simone
name: Gessler, Manfred
name: Wegert, Jenny
name: Kappler, Roland
name: Baumhör, Daniel
name: Burdach, Stefan
name: Kirschner-Schwabe, Renate
name: Kontny, Udo
name: Kulozik, Andreas E.
name: Lohmann, Dietmar
name: Hettmer, Simone
name: Eckert, Cornelia
name: Bielack, Stefan
name: Nathrath, Michaela
name: Niemeyer, Charlotte
name: Richter, Gunther H.
name: Schulte, Johannes
name: Siebert, Reiner
name: Westermann, Frank
name: Molenaar, Jan J.
name: Vassal, Gilles
name: Witt, Hendrik
name: Burkhardt, Birgit
name: Kratz, Christian P.
name: Witt, Olaf
name: Van Tilburg, Cornelis M.
name: Kramm, Christof M.
name: Fleischhack, Gudrun
name: Dirksen, Uta
name: Rutkowski, Stefan
name: Fruhwald, Michael
name: Von Hoff, Katja
name: Wolf, Stephan
name: Klingebiel, Thomas
name: Koscielniak, Ewa
name: Landgraf, Pablo
name: Koster, Jan
name: Resnick, Adam C.
name: Zhang, Jinghui
name: Liu, Yanling
name: Zhou, Xin
name: Waanders, Angela J.
name: Zwijnenburg, Danny A.
name: Raman, Pichai
name: Brors, Benedikt
name: Weber, Ursula D.
name: Northcott, Paul A.
name: Pajtler, Kristian W.
name: Kool, Marcel
name: Piro, Rosario M.
name: Korbel, Jan O.
name: Schlesner, Matthias
name: Eils, Roland
name: Jones, David T. W.
name: Lichter, Peter
name: Chavez, Lukas
name: Zapatka, Marc
name: Pfister, Stefan M.
name: ICGC PedBrain-Seq Project ICGC
Publisher: name: Universität Ulm
Year: 2018
Subjects: subject: Cancer genomics
subject: Oncogenesis
subject: Paediatric cancer
subject: Predictive markers
subject: Translational research
subject: DDC 570 / Life sciences
subject: DDC 610 / Medicine &amp; health
subject: Neoplasms; Genetics
subject: Child
subject: Tumor suppressor protein p53
subject: Krebs
subject: Kind
subject: Jugend
subject: Protein p53

description: 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.