Postzygotic mosaicism of SMARCB1 variants in patients with rhabdoid tumors: A not-so-rare condition exposing to successive tumors

• DOI: 10.1093/neuonc/noae122
• Publication Date: 2024-08-02T16:19:40Z
• Authors: Grégory Thomson; Mathilde Filser; Léa Guerrini-Rous...; Arnault Tauziede-...; Christine Bourneix; Marion Gauthier-V...; Fatoumata Simaga; Kévin Beccaria; Cécile Faure-Conter; Aurélien Maureille; Hélène Zattara-Ca...; Nicolas Andre; Natacha Entz-Werle; Laurence Brugieres; Ludovic Mansuy; Philippe Denizeau; Sophie Julia; Olivier Ingster; Sophie Lejeune; Afane Brahimi; Isabelle Coupier; Valérie Bonadona; Olivier Delattre; Julien Masliah-Pl...; Franck Bourdeaut
• Keywords: SMARCB1

Rhabdoid tumors (RT) are aggressive, rare predominantly affecting young children, characterized by biallelic SMARCB1 gene inactivation. While most alterations acquired de novo, a third of cases exhibit germline alterations, defining Tumors Predisposition Syndrome. With the increased sensitivity next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases more detectable. This study focuses on exploring notably mosaicism blood samples children with RT and parents, using custom NGS panel. A cohort 280 140 parents analysis was studied. Germline DNA from 111 32 were reanalyzed panel 1500X average depth targeting identify intragenic variants not detected conventional low-sensitivity methods. Follow-up data obtained for 77 patients. Nine previously undetected identified, totaling 17/280 patients mosaic variant (6.1%) cohort, allele frequencies between 0.9% 33%, thus highlighting prior underestimation its prevalence. showed that 4 out 7 survivors developed distinct novel tumors, 2 sharing initial tumor, emphasizing potential clinical impact mosaicism. The hitherto underestimated rate underscores need optimized counseling oncological monitoring. findings have significant medical implications, considering dire prognosis RT.