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. 2018 Mar 15;555(7696):321-327.
doi: 10.1038/nature25480. Epub 2018 Feb 28.

The landscape of genomic alterations across childhood cancers

Susanne N Gröbner  1   2   3 , Barbara C Worst  1   2   3   4 , Joachim Weischenfeldt  5   6 , Ivo Buchhalter  7 , Kortine Kleinheinz  7 , Vasilisa A Rudneva  5   8 , Pascal D Johann  1   2   3   4 , Gnana Prakash Balasubramanian  1   2   9 , Maia Segura-Wang  5 , Sebastian Brabetz  1   2   3 , Sebastian Bender  1   2 , Barbara Hutter  3   7   9 , Dominik Sturm  1   2   3   4 , Elke Pfaff  1   2   3   4 , Daniel Hübschmann  4   9   10 , Gideon Zipprich  7 , Michael Heinold  7   10 , Jürgen Eils  7 , Christian Lawerenz  7 , Serap Erkek  1   2   3   5 , Sander Lambo  1   2   3 , Sebastian Waszak  5 , Claudia Blattmann  3   11 , Arndt Borkhardt  3   12 , Michaela Kuhlen  3   12 , Angelika Eggert  3   13 , Simone Fulda  3   14 , Manfred Gessler  15 , Jenny Wegert  15 , Roland Kappler  3   16 , Daniel Baumhoer  17 , Stefan Burdach  3   18 , Renate Kirschner-Schwabe  3   13 , Udo Kontny  3   19 , Andreas E Kulozik  1   3   4 , Dietmar Lohmann  3   20 , Simone Hettmer  21 , Cornelia Eckert  3   13 , Stefan Bielack  11 , Michaela Nathrath  3   18   22 , Charlotte Niemeyer  3   21 , Günther H Richter  3   18 , Johannes Schulte  3   13 , Reiner Siebert  23 , Frank Westermann  3   24 , Jan J Molenaar  25 , Gilles Vassal  26 , Hendrik Witt  1   2   3   4 ; ICGC PedBrain-Seq Project; ICGC MMML-Seq Project; Birgit Burkhardt  27 , Christian P Kratz  28 , Olaf Witt  1   3   4   29 , Cornelis M van Tilburg  1   3   30 , Christof M Kramm  31 , Gudrun Fleischhack  3   32 , Uta Dirksen  32 , Stefan Rutkowski  33 , Michael Frühwald  34 , Katja von Hoff  33 , Stephan Wolf  35 , Thomas Klingebiel  3   36 , Ewa Koscielniak  11 , Pablo Landgraf  37 , Jan Koster  38 , Adam C Resnick  39 , Jinghui Zhang  40 , Yanling Liu  40 , Xin Zhou  40 , Angela J Waanders  41 , Danny A Zwijnenburg  38 , Pichai Raman  39 , Benedikt Brors  3   7   8 , Ursula D Weber  3   42 , Paul A Northcott  2   3   8 , Kristian W Pajtler  1   2   3   4 , Marcel Kool  1   2   3 , Rosario M Piro  3   42   43   44 , Jan O Korbel  5 , Matthias Schlesner  7   45 , Roland Eils  7   10 , David T W Jones  1   2   3 , Peter Lichter  3   42 , Lukas Chavez  1   2   3 , Marc Zapatka  42   43 , Stefan M Pfister  1   2   3   4
Collaborators, Affiliations

The landscape of genomic alterations across childhood cancers

Susanne N Gröbner et al. Nature. .

Erratum in

  • Author Correction: The landscape of genomic alterations across childhood cancers.
    Gröbner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, Johann PD, Balasubramanian GP, Segura-Wang M, Brabetz S, Bender S, Hutter B, Sturm D, Pfaff E, Hübschmann D, Zipprich G, Heinold M, Eils J, Lawerenz C, Erkek S, Lambo S, Waszak S, Blattmann C, Borkhardt A, Kuhlen M, Eggert A, Fulda S, Gessler M, Wegert J, Kappler R, Baumhoer D, Burdach S, Kirschner-Schwabe R, Kontny U, Kulozik AE, Lohmann D, Hettmer S, Eckert C, Bielack S, Nathrath M, Niemeyer C, Richter GH, Schulte J, Siebert R, Westermann F, Molenaar JJ, Vassal G, Witt H, Burkhardt B, Kratz CP, Witt O, van Tilburg CM, Kramm CM, Fleischhack G, Dirksen U, Rutkowski S, Frühwald M, von Hoff K, Wolf S, Klingebiel T, Koscielniak E, Landgraf P, Koster J, Resnick AC, Zhang J, Liu Y, Zhou X, Waanders AJ, Zwijnenburg DA, Raman P, Brors B, Weber UD, Northcott PA, Pajtler KW, Kool M, Piro RM, Korbel JO, Schlesner M, Eils R, Jones DTW, Lichter P, Chavez L, Zapatka M, Pfister SM; ICGC PedBrain-Seq Project; ICGC MMML-Seq Project. Gröbner SN, et al. Nature. 2018 Jul;559(7714):E10. doi: 10.1038/s41586-018-0167-2. Nature. 2018. PMID: 29875405

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.

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