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@ARTICLE{Thomas:168504,
author = {C. Thomas and K. Oehl-Huber and S. Bens and P. Soschinski
and A. Koch and K. Nemes and F. Oyen and U. Kordes and M.
Kool$^*$ and M. C. Frühwald and M. Hasselblatt and R.
Siebert},
title = {{T}ransposable element insertion as a mechanism of
{SMARCB}1 inactivation in atypical teratoid/rhabdoid tumor.},
journal = {Genes, chromosomes $\&$ cancer},
volume = {60},
number = {8},
issn = {1098-2264},
address = {New York, NY},
publisher = {Wiley-Liss},
reportid = {DKFZ-2021-00936},
pages = {586-590},
year = {2021},
note = {2021 Aug;60(8):586-590},
abstract = {Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant
brain tumor predominantly occurring in infants. Biallelic
SMARCB1 mutations causing loss of nuclear SMARCB1/INI1
protein expression represent the characteristic genetic
lesion. Pathogenic SMARCB1 mutations comprise single
nucleotide variants, small insertions/deletions, large
deletions, which may be also present in the germline
(rhabdoid tumor predisposition syndrome 1), as well as
somatic copy-number neutral loss of heterozygosity (LOH). In
some SMARCB1-deficient AT/RT underlying biallelic mutations
cannot be identified. Here we report the case of a
24-months-old girl diagnosed with a large brain tumor. The
malignant rhabdoid tumor showed loss of nuclear SMARCB1/INI1
protein expression and the diagnosis of AT/RT was confirmed
by DNA methylation profiling. While FISH, MLPA, Sanger
sequencing and DNA methylation data-based imbalance analysis
did not disclose alterations affecting SMARCB1, OncoScan
array analysis revealed a 28.29 Mb sized region of
copy-number neutral LOH on chromosome 22q involving the
SMARCB1 locus. Targeted next-generation sequencing did also
not detect a single nucleotide variant but instead revealed
insertion of an AluY element into exon 2 of SMARCB1.
Specific PCR-based Sanger sequencing verified the Alu
insertion (SMARCB1 $c.199_200$ Alu ins) resulting in a
frame-shift truncation not present in the patient's
germline. In conclusion, transposable element insertion
represents a hitherto not widely recognized mechanism of
SMARCB1 disruption in AT/RT, which might not be detected by
several widely applied conventional diagnostics assays. This
finding has particular clinical implications, if rhabdoid
predisposition syndrome 1 is suspected, but germline SMARCB1
alterations cannot be identified. This article is protected
by copyright. All rights reserved.},
keywords = {Alu element (Other) / SMARCB1 (Other) / transposable
element insertion (Other) / typical teratoid/rhabdoid tumor
(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:33896072},
doi = {10.1002/gcc.22954},
url = {https://inrepo02.dkfz.de/record/168504},
}