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@ARTICLE{Holdhof:166501,
author = {D. Holdhof and P. D. Johann$^*$ and M. Spohn and M.
Bockmayr and S. Safaei and P. Joshi$^*$ and J.
Masliah-Planchon and B. Ho and M. Andrianteranagna and F.
Bourdeaut and A. Huang and M. Kool$^*$ and S. A. Upadhyaya
and A. E. Bendel and D. Indenbirken and W. D. Foulkes and J.
W. Bush and D. Creytens and U. Kordes and M. C. Frühwald
and M. Hasselblatt and U. Schüller},
title = {{A}typical teratoid/rhabdoid tumors ({ATRT}s) with
{SMARCA}4 mutation are molecularly distinct from
{SMARCB}1-deficient cases.},
journal = {Acta neuropathologica},
volume = {142},
number = {2},
issn = {1432-0533},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2020-02944},
pages = {291-301},
year = {2021},
note = {2021 Feb;141(2):291-301},
abstract = {Atypical teratoid/rhabdoid tumors (ATRTs) are very
aggressive childhood malignancies of the central nervous
system. The underlying genetic cause are inactivating
bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4.
ATRT-SMARCA4 have been associated with a higher frequency of
germline mutations, younger age, and an inferior prognosis
in comparison to SMARCB1 mutated cases. Based on their DNA
methylation profiles and transcriptomics, SMARCB1 mutated
ATRTs have been divided into three distinct molecular
subgroups: ATRT-TYR, ATRT-SHH, and ATRT-MYC. These subgroups
differ in terms of age at diagnosis, tumor location, type of
SMARCB1 alterations, and overall survival. ATRT-SMARCA4 are,
however, less well understood, and it remains unknown,
whether they belong to one of the described ATRT subgroups.
Here, we examined 14 ATRT-SMARCA4 by global DNA methylation
analyses. We show that they form a separate group
segregating from SMARCB1 mutated ATRTs and from other
SMARCA4-deficient tumors like small cell carcinoma of the
ovary, hypercalcemic type (SCCOHT) or SMARCA4 mutated
extra-cranial malignant rhabdoid tumors. In contrast,
medulloblastoma (MB) samples with heterozygous SMARCA4
mutations do not group separately, but with established MB
subgroups. RNA sequencing of ATRT-SMARCA4 confirmed the
clustering results based on DNA methylation profiling and
displayed an absence of typical signature genes upregulated
in SMARCB1 deleted ATRT. In summary, our results suggest
that, in line with previous clinical observations,
ATRT-SMARCA4 should be regarded as a distinct molecular
subgroup.},
keywords = {ATRT (Other) / BRG1 (Other) / DNA methylation (Other) / RNA
sequencing (Other) / Rhabdoid (Other) / SMARCA4 (Other)},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33331994},
doi = {10.1007/s00401-020-02250-7},
url = {https://inrepo02.dkfz.de/record/166501},
}