%0 Journal Article
%A Frühwald, Michael C
%A Hasselblatt, Martin
%A Nemes, Karolina
%A Bens, Susanne
%A Steinbügl, Mona
%A Johann, Pascal D
%A Kerl, Kornelius
%A Hauser, Peter
%A Quiroga, Eduardo
%A Solano-Paez, Palma
%A Biassoni, Veronica
%A Gil-da-Costa, Maria Joao
%A Perek-Polnik, Martha
%A van de Wetering, Marianne
%A Sumerauer, David
%A Pears, Jane
%A Stabell, Niklas
%A Holm, Stefan
%A Hengartner, Heinz
%A Gerber, Nicolas U
%A Grotzer, Michael
%A Boos, Joachim
%A Ebinger, Martin
%A Tippelt, Stefan
%A Paulus, Werner
%A Furtwängler, Rhoikos
%A Hernáiz-Driever, Pablo
%A Reinhard, Harald
%A Rutkowski, Stefan
%A Schlegel, Paul-Gerhardt
%A Schmid, Irene
%A Kortmann, Rolf-Dieter
%A Timmermann, Beate
%A Warmuth-Metz, Monika
%A Kordes, Uwe
%A Gerss, Joachim
%A Nysom, Karsten
%A Schneppenheim, Reinhard
%A Siebert, Reiner
%A Kool, Marcel
%A Graf, Norbert
%T Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors.
%D 2020
%U http://hdl.handle.net/10668/14897
%X Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009-2017). Therapy consisted of surgery, anthracycline-based induction, and either radiotherapy or high dose chemotherapy following a consensus among European experts. Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and sequencing were employed for assessment of somatic and germline mutations in SWItch/sucrose nonfermentable related, matrix associated, actin dependent regulator of chromatin, subfamily B (SMARCB1). Molecular subgroups (ATRT-SHH, ATRT-TYR, and ATRT-MYC) were determined using DNA methylation arrays, resulting in profiles of 84 tumors. Median age at diagnosis of 67 girls and 76 boys was 29.5 months. Five-year overall survival (OS) and event-free survival (EFS) were 34.7 ± 4.5% and 30.5 ± 4.2%, respectively. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRTs (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC (17/84). Age  Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.
%K ATRT
%K DNA methylation profiling
%K European Rhabdoid Tumor Registry
%K SMARCB1
%K prognosis
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