Journal Article

DKFZ-2022-00779

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SMARCB1-deficient and SMARCA4-deficient Malignant Brain Tumors With Complex Copy Number Alterations andTP53Mutations May Represent the First Clinical Manifestation of Li-Fraumeni Syndrome.

Hasselblatt, M. ; Thomas, C. ; Federico, A.DKFZ* ; Nemes, K. ; Johann, P. D.DKFZ* ; Bison, B. ; Bens, S. ; Dahlum, S. ; Kordes, U. ; Redlich, A. ; Lessel, L. ; Pajtler, K. W.DKFZ* ; Mawrin, C. ; Schüller, U. ; Nolte, K. ; Kramm, C. M. ; Hinz, F. ; Sahm, F. ; Giannini, C. ; Penkert, J. ; Kratz, C. P. ; Pfister, S. M.DKFZ* ; Siebert, R. ; Paulus, W. ; Kool, M.DKFZ* ; Frühwald, M. C.

2022
Ovid [S.l.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1097/PAS.0000000000001905

Abstract: Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant central nervous system tumor predominantly affecting infants. Mutations ofSMARCB1or (rarely)SMARCA4causing loss of nuclear SMARCB1 or SMARCA4 protein expression are characteristic features, but further recurrent genetic alterations are lacking. Most AT/RTs occur de novo, but secondary AT/RTs arising from other central nervous system tumors have been reported. Malignant gliomas, IDH wild-type, arising in patients with Li-Fraumeni syndrome typically show somatic mutations ofTP53as well as complex copy number alterations, but little is known about the loss of SMARCB1 or SMARCA4 protein expression in this context. Here, we report 2 children in whom malignant supratentorial brain tumors with SMARCB1 deficiency, complex copy number alterations, and somaticTP53mutations lead to the discovery of pathogenic/likely pathogenicTP53variants in the germline. Screening of the molecularneuropathology.org dataset for cases with similar genetic and epigenetic alterations yielded another case with SMARCA4 deficiency in a young adult with Li-Fraumeni syndrome. In conclusion, SMARCB1-deficient or SMARCA4-deficient malignant brain tumors with complex copy number alterations and somaticTP53mutations in children and young adults may represent the first clinical manifestation of Li-Fraumeni syndrome and should prompt genetic counseling and investigation forTP53germline status.

Note: 2022 Sep 1;46(9):1277-1283

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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