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The landscape of genomic alterations across childhood cancers

Nature (London), 2018-03, Vol.555 (7696), p.321-327 [Peer Reviewed Journal]

COPYRIGHT 2018 Nature Publishing Group ;COPYRIGHT 2018 Nature Publishing Group ;Copyright Nature Publishing Group Mar 15, 2018 ;Distributed under a Creative Commons Attribution 4.0 International License ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/nature25480 ;PMID: 29489754

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Title:
The landscape of genomic alterations across childhood cancers
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
Subjects: Adolescent ; Adolescents ; Adult ; Adults ; Bioinformatics ; Cancer ; Cancer in children ; Cancer research ; Child ; Childhood cancer ; Children ; Chromothripsis ; Clinical trials ; Cohort Studies ; Diploidy ; DNA Copy Number Variations - genetics ; Gene mutation ; Gene mutations ; Genes ; Genetic analysis ; Genetic aspects ; Genetic Predisposition to Disease - genetics ; Genome, Human - genetics ; Genomes ; Genomics ; Germ-Line Mutation - genetics ; Health aspects ; Humans ; Life Sciences ; Medical research ; Molecular Targeted Therapy ; Mutation ; Mutation - genetics ; Mutation Rate ; Neoplasms ; Neoplasms - classification ; Neoplasms - drug therapy ; Neoplasms - genetics ; Oncology, Experimental ; p53 Protein ; Signatures ; Studies ; Tumor Suppressor Protein p53 - genetics ; Tumors ; Workflow ; Young Adult ; Young adults
Is Part Of: Nature (London), 2018-03, Vol.555 (7696), p.321-327
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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0028-0836
EISSN: 1476-4687
DOI: 10.1038/nature25480
PMID: 29489754
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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The landscape of genomic alterations across childhood cancers

COPYRIGHT 2018 Nature Publishing Group ;COPYRIGHT 2018 Nature Publishing Group ;Copyright Nature Publishing Group Mar 15, 2018 ;Distributed under a Creative Commons Attribution 4.0 International License ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/nature25480 ;PMID: 29489754

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