Back
Full-text
Journal article

The landscape of genomic alterations across childhood cancers.

  • Gröbner SN Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Worst BC Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Weischenfeldt J European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Buchhalter I Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kleinheinz K Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Rudneva VA European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Johann PD Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Balasubramanian GP Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Segura-Wang M European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Brabetz S Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Bender S Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Hutter B German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Sturm D Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Pfaff E Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Hübschmann D Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
  • Zipprich G Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Heinold M Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Eils J Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Lawerenz C Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Erkek S Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Lambo S Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Waszak S European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Blattmann C German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Borkhardt A German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kuhlen M German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Eggert A German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Fulda S German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gessler M Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
  • Wegert J Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
  • Kappler R German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Baumhoer D Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Burdach S German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kirschner-Schwabe R German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kontny U German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kulozik AE Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Lohmann D German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Hettmer S Division of Pediatric Hematology and Oncology, Department of Pediatrics, University Medical Center Freiburg, Freiburg, Germany.
  • Eckert C German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Bielack S Klinikum Stuttgart - Olgahospital, Zentrum für Kinder-, Jugend- und Frauenmedizin, Pädiatrie, Stuttgart, Germany.
  • Nathrath M German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Niemeyer C German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Richter GH German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schulte J German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Siebert R Institute of Human Genetics, University of Ulm & University Hospital of Ulm, Ulm, Germany.
  • Westermann F German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Molenaar JJ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • Vassal G Innovative Therapies for Children with Cancer Consortium and Department of Clinical Research, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
  • Witt H Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Burkhardt B Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Kratz CP Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Witt O Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
  • van Tilburg CM German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kramm CM Pediatric Oncology & Hematology, Pediatrics III, University Hospital of Essen, Essen, Germany.
  • Fleischhack G Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Dirksen U Swabian Children's Cancer Center, Children's Hospital, Klinikum Augsburg, Augsburg, Germany.
  • Rutkowski S Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Frühwald M Genomics and Proteomics Core Facility, High Throughput Sequencing Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • von Hoff K German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Wolf S Klinikum Stuttgart - Olgahospital, Zentrum für Kinder-, Jugend- und Frauenmedizin, Pädiatrie, Stuttgart, Germany.
  • Klingebiel T University Hospital Cologne, Klinik und Poliklinik für Kinder- und Jugendmedizin, Cologne, Germany.
  • Koscielniak E Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands.
  • Landgraf P Division of Neurosurgery, Center for Childhood Cancer Research, Department of Biomedical and Health Informatics and Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Koster J Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Resnick AC Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Zhang J Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Liu Y Division of Oncology, Center for Childhood Cancer Research, Department of Biomedical and Health Informatics and Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, USA.
  • Zhou X Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands.
  • Waanders AJ Division of Neurosurgery, Center for Childhood Cancer Research, Department of Biomedical and Health Informatics and Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Zwijnenburg DA German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Raman P German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Brors B Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Weber UD Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Northcott PA Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Pajtler KW German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kool M European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Piro RM Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Korbel JO Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schlesner M Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Eils R German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jones DTW Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Lichter P Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Chavez L Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Zapatka M
  • Pfister SM
Show more…
  • 2018-03-01
Published in:
  • Nature. - 2018
Adolescent
Adult
Child
Chromothripsis
Cohort Studies
DNA Copy Number Variations
Diploidy
Genetic Predisposition to Disease
Genome, Human
Genomics
Germ-Line Mutation
Humans
Molecular Targeted Therapy
Mutation
Mutation Rate
Neoplasms
Tumor Suppressor Protein p53
Young Adult
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/73302
Statistics
Document views: 86 File downloads:
  • Full-text: 0