Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC Subgroup
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Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC Subgroup. / 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.
in: AM J SURG PATHOL, Jahrgang 42, Nr. 4, 04.2018, S. 506-511.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC Subgroup
AU - Johann, Pascal D
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 M
AU - Schneppenheim, Reinhard
AU - Siebert, Reiner
AU - Frühwald, Michael C
AU - Paulus, Werner
AU - Kool, Marcel
AU - Hasselblatt, Martin
PY - 2018/4
Y1 - 2018/4
N2 - 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.
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.
KW - Journal Article
U2 - 10.1097/PAS.0000000000001023
DO - 10.1097/PAS.0000000000001023
M3 - SCORING: Journal article
C2 - 29324471
VL - 42
SP - 506
EP - 511
JO - AM J SURG PATHOL
JF - AM J SURG PATHOL
SN - 0147-5185
IS - 4
ER -
