%0 Journal Article
%A Thomas, Christian
%A Oehl-Huber, Kathrin
%A Bens, Susanne
%A Soschinski, Patrick
%A Koch, Arend
%A Nemes, Karolina
%A Oyen, Florian
%A Kordes, Uwe
%A Kool, Marcel
%A Frühwald, Michael C
%A Hasselblatt, Martin
%A Siebert, Reiner
%T Transposable element insertion as a mechanism of SMARCB1 inactivation in atypical teratoid/rhabdoid tumor.
%J Genes, chromosomes & cancer
%V 60
%N 8
%@ 1098-2264
%C New York, NY
%I Wiley-Liss
%M DKFZ-2021-00936
%P 586-590
%D 2021
%Z 2021 Aug;60(8):586-590
%X 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.
%K Alu element (Other)
%K SMARCB1 (Other)
%K transposable element insertion (Other)
%K typical teratoid/rhabdoid tumor (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33896072
%R 10.1002/gcc.22954
%U https://inrepo02.dkfz.de/record/168504