RT Journal Article
T1 Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors.
A1 Frühwald, Michael C
A1 Hasselblatt, Martin
A1 Nemes, Karolina
A1 Bens, Susanne
A1 Steinbügl, Mona
A1 Johann, Pascal D
A1 Kerl, Kornelius
A1 Hauser, Peter
A1 Quiroga, Eduardo
A1 Solano-Paez, Palma
A1 Biassoni, Veronica
A1 Gil-da-Costa, Maria Joao
A1 Perek-Polnik, Martha
A1 van de Wetering, Marianne
A1 Sumerauer, David
A1 Pears, Jane
A1 Stabell, Niklas
A1 Holm, Stefan
A1 Hengartner, Heinz
A1 Gerber, Nicolas U
A1 Grotzer, Michael
A1 Boos, Joachim
A1 Ebinger, Martin
A1 Tippelt, Stefan
A1 Paulus, Werner
A1 Furtwängler, Rhoikos
A1 Hernáiz-Driever, Pablo
A1 Reinhard, Harald
A1 Rutkowski, Stefan
A1 Schlegel, Paul-Gerhardt
A1 Schmid, Irene
A1 Kortmann, Rolf-Dieter
A1 Timmermann, Beate
A1 Warmuth-Metz, Monika
A1 Kordes, Uwe
A1 Gerss, Joachim
A1 Nysom, Karsten
A1 Schneppenheim, Reinhard
A1 Siebert, Reiner
A1 Kool, Marcel
A1 Graf, Norbert
K1 ATRT
K1 DNA methylation profiling
K1 European Rhabdoid Tumor Registry
K1 SMARCB1
K1 prognosis
AB 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.
YR 2020
FD 2020
LK http://hdl.handle.net/10668/14897
UL http://hdl.handle.net/10668/14897
LA en
DS RISalud
RD Apr 6, 2025