@article{f645ada6f7c34565b427cbf7960f48e6,
title = "The landscape of genomic alterations across childhood cancers",
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.",
keywords = "Adolescent, Adult, Child, Chromothripsis, Cohort Studies, DNA Copy Number Variations/genetics, Diploidy, Genetic Predisposition to Disease/genetics, Genome, Human/genetics, Genomics, Germ-Line Mutation/genetics, Humans, Molecular Targeted Therapy, Mutation/genetics, Mutation Rate, Neoplasms/classification, Tumor Suppressor Protein p53/genetics, Young Adult",
author = "Gr{\"o}bner, {Susanne N} and Worst, {Barbara C} and Joachim Weischenfeldt and Ivo Buchhalter and Kortine Kleinheinz and Rudneva, {Vasilisa A} and Johann, {Pascal D} and Balasubramanian, {Gnana Prakash} and Maia Segura-Wang and Sebastian Brabetz and Sebastian Bender and Barbara Hutter and Dominik Sturm and Elke Pfaff and Daniel H{\"u}bschmann and Gideon Zipprich and Michael Heinold and J{\"u}rgen Eils and Christian Lawerenz and Serap Erkek and Sander Lambo and Sebastian Waszak and Claudia Blattmann and Arndt Borkhardt and Michaela Kuhlen and Angelika Eggert and Simone Fulda and Manfred Gessler and Jenny Wegert and Roland Kappler and Daniel Baumhoer and Stefan Burdach and Renate Kirschner-Schwabe and Udo Kontny and Kulozik, {Andreas E} and Dietmar Lohmann and Simone Hettmer and Cornelia Eckert and Stefan Bielack and Michaela Nathrath and Charlotte Niemeyer and Richter, {G{\"u}nther H} and Johannes Schulte and Reiner Siebert and Frank Westermann and Molenaar, {Jan J} and Gilles Vassal and Hendrik Witt and Birgit Burkhardt and Kratz, {Christian P} and {ICGC PedBrain-Seq Project}",
year = "2018",
month = mar,
day = "15",
doi = "10.1038/nature25480",
language = "English",
volume = "555",
pages = "321--327",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7696",
}
