Groebner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim ORCID: 0000-0002-3917-5524, Buchhalter, Ivo ORCID: 0000-0003-0764-5832, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia ORCID: 0000-0003-2424-618X, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik ORCID: 0000-0003-0250-1696, Pfaff, Elke, Huebschmann, Daniel ORCID: 0000-0002-6041-7049, Zipprich, Gideon, Heinold, Michael, Eils, Jurgen, Lawerenz, Christian, Erkek, Serap ORCID: 0000-0003-4439-5203, Lambo, Sander, Waszak, Sebastian ORCID: 0000-0003-3042-9521, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone ORCID: 0000-0002-0459-6417, Gessler, Manfred ORCID: 0000-0002-7915-6045, Wegert, Jenny, Kappler, Roland ORCID: 0000-0002-8581-2803, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate ORCID: 0000-0001-6335-3274, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Gunther 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, Fruhwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan ORCID: 0000-0002-0890-7585, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Brors, Benedikt ORCID: 0000-0001-5940-3101, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W. ORCID: 0000-0002-3562-6121, Kool, Marcel, Piro, Rosario M. ORCID: 0000-0002-3066-7397, Korbel, Jan O., Schlesner, Matthias ORCID: 0000-0002-5896-4086, Eils, Roland ORCID: 0000-0002-0034-4036, Jones, David T. W., Lichter, Peter, Chavez, Lukas ORCID: 0000-0002-8718-8848, Zapatka, Marc ORCID: 0000-0001-8287-5967 and Pfister, Stefan M. (2018). The landscape of genomic alterations across childhood cancers. Nature, 555 (7696). S. 321 - 344. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Groebner, Susanne N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worst, Barbara C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weischenfeldt, JoachimUNSPECIFIEDorcid.org/0000-0002-3917-5524UNSPECIFIED
Buchhalter, IvoUNSPECIFIEDorcid.org/0000-0003-0764-5832UNSPECIFIED
Kleinheinz, KortineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudneva, Vasilisa A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johann, Pascal D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balasubramanian, Gnana PrakashUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Segura-Wang, MaiaUNSPECIFIEDorcid.org/0000-0003-2424-618XUNSPECIFIED
Brabetz, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bender, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hutter, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sturm, DominikUNSPECIFIEDorcid.org/0000-0003-0250-1696UNSPECIFIED
Pfaff, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebschmann, DanielUNSPECIFIEDorcid.org/0000-0002-6041-7049UNSPECIFIED
Zipprich, GideonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinold, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eils, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lawerenz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erkek, SerapUNSPECIFIEDorcid.org/0000-0003-4439-5203UNSPECIFIED
Lambo, SanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waszak, SebastianUNSPECIFIEDorcid.org/0000-0003-3042-9521UNSPECIFIED
Blattmann, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borkhardt, ArndtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhlen, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggert, AngelikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fulda, SimoneUNSPECIFIEDorcid.org/0000-0002-0459-6417UNSPECIFIED
Gessler, ManfredUNSPECIFIEDorcid.org/0000-0002-7915-6045UNSPECIFIED
Wegert, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kappler, RolandUNSPECIFIEDorcid.org/0000-0002-8581-2803UNSPECIFIED
Baumhoer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burdach, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirschner-Schwabe, RenateUNSPECIFIEDorcid.org/0000-0001-6335-3274UNSPECIFIED
Kontny, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kulozik, Andreas E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohmann, DietmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hettmer, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckert, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bielack, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathrath, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niemeyer, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, Gunther H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siebert, ReinerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westermann, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molenaar, Jan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vassal, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burkhardt, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kratz, Christian P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Tilburg, Cornelis M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramm, Christof M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fleischhack, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dirksen, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rutkowski, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fruhwald, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Hoff, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klingebiel, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koscielniak, EwaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landgraf, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koster, JanUNSPECIFIEDorcid.org/0000-0002-0890-7585UNSPECIFIED
Resnick, Adam C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, JinghuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, YanlingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, XinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waanders, Angela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zwijnenburg, Danny A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raman, PichaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brors, BenediktUNSPECIFIEDorcid.org/0000-0001-5940-3101UNSPECIFIED
Weber, Ursula D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Northcott, Paul A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pajtler, Kristian W.UNSPECIFIEDorcid.org/0000-0002-3562-6121UNSPECIFIED
Kool, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piro, Rosario M.UNSPECIFIEDorcid.org/0000-0002-3066-7397UNSPECIFIED
Korbel, Jan O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesner, MatthiasUNSPECIFIEDorcid.org/0000-0002-5896-4086UNSPECIFIED
Eils, RolandUNSPECIFIEDorcid.org/0000-0002-0034-4036UNSPECIFIED
Jones, David T. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lichter, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chavez, LukasUNSPECIFIEDorcid.org/0000-0002-8718-8848UNSPECIFIED
Zapatka, MarcUNSPECIFIEDorcid.org/0000-0001-8287-5967UNSPECIFIED
Pfister, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-192688
DOI: 10.1038/nature25480
Journal or Publication Title: Nature
Volume: 555
Number: 7696
Page Range: S. 321 - 344
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACUTE LYMPHOBLASTIC-LEUKEMIA; MUTATIONAL PROCESSES; PEDIATRIC CANCER; COPY NUMBER; DISTINCT SUBGROUPS; SOMATIC MUTATIONS; SIGNATURES; REVEALS; TARGET; FUSIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19268

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