Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC Subgroup. (April 2018)

• Record Type: Journal Article
• Authors: Johann, Pascal D.; Bens, Susanne; Oyen, Florian; Wagener, Rabea; Giannini, Caterina; Perry, Arie; Raisanen, Jack M.; Reis, Gerald F.; Nobusawa, Sumihito; Arita, Kazunori; Felsberg, Jörg; Reifenberger, Guido; Agaimy, Abbas; Buslei, Rolf; Capper, David; Pfister, Stefan M.; Schneppenheim, Reinhard; Siebert, Reiner; Frühwald, Michael C.; Paulus, Werner; Kool, Marcel; Hasselblatt, Martin
• Is Part Of: American journal of surgical pathology. Volume 42:Number 4(2018)
• Publication Date: 2018-04
• Subjects: atypical teratoid/rhabdoid tumor -- pituitary -- SMARCB1/INI1 -- DNA methylation profiling -- outcome; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001023
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.