TY  - JOUR
AU  - Johann, Pascal
AU  - Altendorf, Lea
AU  - Efremova, Emma-Maria
AU  - Holsten, Till
AU  - Steinbügl, Mona
AU  - Nemes, Karolina
AU  - Eckhardt, Alicia
AU  - Kresbach, Catena
AU  - Bockmayr, Michael
AU  - Koch, Arend
AU  - Haberler, Christine
AU  - Antonelli, Manila
AU  - DeSisto, John
AU  - Schuhmann, Martin U
AU  - Hauser, Peter
AU  - Siebert, Reiner
AU  - Bens, Susanne
AU  - Kool, Marcel
AU  - Green, Adam L
AU  - Hasselblatt, Martin
AU  - Frühwald, Michael C
AU  - Schüller, Ulrich
TI  - Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.
JO  - Acta neuropathologica
VL  - 146
IS  - 3
SN  - 0001-6322
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2023-01450
SP  - 527-541
PY  - 2023
N1  - #EA:B062# / 2023 Sep;146(3):527-541
AB  - Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18
KW  - AT/RT (Other)
KW  - DNA methylation (Other)
KW  - Pediatric cancer (Other)
KW  - RNA sequencing (Other)
KW  - Recurrent tumor (Other)
KW  - Rhabdoid tumor (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37450044
DO  - DOI:10.1007/s00401-023-02608-7
UR  - https://inrepo02.dkfz.de/record/277733
ER  -