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The landscape of genomic alterations across childhood cancers

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  • 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
  • Birgit Burkhardt
  • Christian P Kratz
  • ICGC PedBrain-Seq Project
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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.

Original languageEnglish
JournalNature
Volume555
Issue number7696
Pages (from-to)321-327
Number of pages7
ISSN0028-0836
DOIs
Publication statusPublished - 15 Mar 2018

    Research areas

  • Journal Article

ID: 53453023