Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC Subgroup

Pascal D. Johann, Susanne Bens, Florian Oyen, Rabea Wagener, Caterina Giannini, Arie Perry, Jack M. Raisanen, Gerald F. Reis, Sumihito Nobusawa, Kazunori Arita, Jörg Felsberg, Guido Reifenberger, Abbas Agaimy, Rolf Buslei, David Capper, Stefan M. Pfister, Reinhard Schneppenheim, Reiner Siebert, Michael C. Frühwald, Werner PaulusMarcel Kool, Martin Hasselblatt

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

40 Citaten (Scopus)


Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly encountered in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. A small group of ATRT stands out clinically, because these tumors are located in the sellar region of adults. To investigate if sellar region ATRT in adults represents a molecular distinct entity, we characterized molecular alterations in 7 sellar region ATRTs in adults as compared with 150 pediatric ATRTs and 47 pituitary adenomas using SMARCB1 sequencing, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization as well as DNA methylation profiling. The median age of the 6 female and 1 male patients was 56 years. On histopathologic examination, all tumors were malignant rhabdoid tumors showing loss of SMARCB1/INI1 protein expression. Two cases displayed compound heterozygous SMARCB1 point mutations, 3 cases showed heterozygous SMARCB1 deletions with point mutations of the other allele and 1 case a homozygous SMARCB1 deletion; in 1 case, underlying SMARCB1 alterations could not be identified. On unsupervised hierarchical cluster analysis of DNA methylation profiles, sellar region ATRTs did not form a distinct group, but clustered with ATRT-MYC, 1 of 3 recently described molecular subgroups of ATRT. On analysis of DNA methylation array intensity data, only 1 sellar region ATRT showed characteristic features of pediatric ATRT-MYC, that is, major copy number losses affecting the SMARCB1 region. In conclusion, these results suggest that sellar region ATRTs in adults form a clinically distinct entity with a different mutational spectrum, but epigenetic similarities with pediatric ATRTs of the ATRT-MYC subgroup.

Originele taal-2Engels
Pagina's (van-tot)506-511
Aantal pagina's6
TijdschriftAmerican Journal of Surgical Pathology
Nummer van het tijdschrift4
StatusGepubliceerd - 2018
Extern gepubliceerdJa


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