TY  - JOUR
AU  - Johann, Pascal
AU  - Bens, Susanne
AU  - Oyen, Florian
AU  - Wagener, Rabea
AU  - Giannini, Caterina
AU  - Perry, Arie
AU  - Raisanen, Jack M
AU  - Reis, Gerald F
AU  - Nobusawa, Sumihito
AU  - Arita, Kazunori
AU  - Felsberg, Jörg
AU  - Reifenberger, Guido
AU  - Agaimy, Abbas
AU  - Buslei, Rolf
AU  - Capper, David
AU  - Pfister, Stefan
AU  - Schneppenheim, Reinhard
AU  - Siebert, Reiner
AU  - Frühwald, Michael C
AU  - Paulus, Werner
AU  - Kool, Marcel
AU  - Hasselblatt, Martin
TI  - Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC Subgroup.
JO  - The American journal of surgical pathology
VL  - 42
IS  - 4
SN  - 0147-5185
CY  - Philadelphia, Pa.
PB  - Lippincott Williams & Wilkins
M1  - DKFZ-2018-00464
SP  - 506 - 511
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29324471
DO  - DOI:10.1097/PAS.0000000000001023
UR  - https://inrepo02.dkfz.de/record/132820
ER  -