Author:
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.,
Abstract
Abstract
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.
Publisher
Springer Science and Business Media LLC