Molecular transition of an adult low-grade brain tumor to an atypical teratoid/rhabdoid tumor over a time-course of 14 years

• Verfasst von: Schweizer, Yvonne [VerfasserIn]
• Verfasst von: Kölsche, Christian [VerfasserIn]
• Verfasst von: Schrimpf, Daniel [VerfasserIn]
• Verfasst von: Brehmer, Stefanie [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Kerl, Hans Ulrich [VerfasserIn]
• Verfasst von: Seiz-Rosenhagen, Marcel [VerfasserIn]
• Titel: Molecular transition of an adult low-grade brain tumor to an atypical teratoid/rhabdoid tumor over a time-course of 14 years
• Verf.angabe: Yvonne Schweizer, MD, Zsolt Meszaros, MD, David T.W. Jones, PhD, Christian Koelsche, MD, Miream Boudalil, Petra Fiesel, MSc, Daniel Schrimpf, PhD, Rosario M. Piro, PhD, Stefanie Brehmer, MD, Andreas von Deimling, MD, Ulrich Kerl, MD, Marcel Seiz-Rosenhagen, MD, and David Capper, MD
• E-Jahr: 2017
• Jahr: 14 July 2017
• Umfang: 10 S.
• Fussnoten: Gesehen am 16.07.2018
• Titel Quelle: Enthalten in: Journal of neuropathology and experimental neurology
• Ort Quelle: Oxford : Oxford University Press, 1942
• Jahr Quelle: 2017
• Band/Heft Quelle: 76(2017), 8, Seite 655-664
• ISSN Quelle: 1554-6578
• DOI: doi:10.1093/jnen/nlx044
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 157762016X

Abstract

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant, pediatric brain tumor typically arising de novo. Inactivation of SMARCB1 is a defining molecular event. We present here a rare case of an adult (35 years) low-grade SMARCB1-deleted brain tumor with transition into prototypical AT/RT over 14 years. Molecular analysis was performed for 3 tumor presentations including copy number analysis, DNA methylation analysis (450k), and whole exome sequencing. We detected the identical somatic SMARCB1 deletion at all 3 time-points. In an unsupervised hierarchical clustering of methylation data together with 127 reference cases comprising 9 brain tumor classes all 3 manifestations clustered with AT/RT. Exome sequencing revealed an increase of mutational burden over time. The acquired mutations and additional copy number changes did not affect known cancer genes. In conclusion, we demonstrate molecular changes associated with histological and clinical transition of a low-grade brain tumor to an adult AT/RT. Our observation of a stable disease course for nearly 10 years in a tumor with SMARCB1 loss and an AT/RT-like DNA methylation profile indicates that caution may be required in the diagnostic interpretation of such findings in adult patients.