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ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC
Most atypical teratoid/rhabdoid tumors (ATRTs) occur in infants, but children and adolescents may also be affected. ATRTs occurring in older patients often comprise the molecular subgroup ATRT-MYC. Recently, central nervous system low-grade diffusely infiltrative tumor with INI1 deficiency (CNS LGDI...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165080/ http://dx.doi.org/10.1093/neuonc/noac079.006 |
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author | Thomas, Christian Federico, Aniello Bens, Susanne Hellström, Mats Casar-Borota, Olivera Kordes, Uwe Neumann, Julia E Dottermusch, Matthias Rodriguez, Fausto E Lo, Andrea C Cheng, Sylvia Hendson, Glenda Hukin, Juliette Hartmann, Christian Koch, Arend Capper, David Siebert, Reiner Paulus, Werner Nemes, Karolina Johann, Pascal D Frühwald, Michael C Kool, Marcel Hasselblatt, Martin |
author_facet | Thomas, Christian Federico, Aniello Bens, Susanne Hellström, Mats Casar-Borota, Olivera Kordes, Uwe Neumann, Julia E Dottermusch, Matthias Rodriguez, Fausto E Lo, Andrea C Cheng, Sylvia Hendson, Glenda Hukin, Juliette Hartmann, Christian Koch, Arend Capper, David Siebert, Reiner Paulus, Werner Nemes, Karolina Johann, Pascal D Frühwald, Michael C Kool, Marcel Hasselblatt, Martin |
author_sort | Thomas, Christian |
collection | PubMed |
description | Most atypical teratoid/rhabdoid tumors (ATRTs) occur in infants, but children and adolescents may also be affected. ATRTs occurring in older patients often comprise the molecular subgroup ATRT-MYC. Recently, central nervous system low-grade diffusely infiltrative tumor with INI1 deficiency (CNS LGDIT-INI1) has been described as a rare low-grade lesion (Nobusawa et al. Am J Surg Pathol 2020;44:1459-1468). Little is known on the molecular relationship of CNS LGDIT-INI1 and ATRT. We therefore further explored a series of six CNS LGDIT-INI1. The median age of the four males and two females was 16 years (range: 10-28 years). All tumors were of supratentorial location and showed low to moderate cellularity, diffuse growth of inconspicuous small SMARCB1-deficient tumor cells and reactive pleomorphic neuronal and glial cells with retained SMARCB1-staining in the background. In addition, two cases also displayed a high-grade rhabdoid component. After DNA isolation, purification and bisulfite conversion, samples were subjected to DNA methylation profiling (MethylationEPIC BeadChip array). Using DNA methylation-based classification and the Heidelberg Brain Tumor Classifier (version v11b4), all tumors were classified as ATRT-MYC (median calibrated score: 0.97). On t-SNE analysis, DNA methylation profiles grouped closely together in proximity to ATRT-MYC. Follow-up information was available for four cases (including the two cases with a high-grade component). Patients received heterogeneous treatments (including chemotherapy according to AT/RT protocols) and experienced stable disease or complete remission after an observation time of three to 56 months. In conclusion, CNS LGDIT-INI1 is a clinically and histologically distinct entity with relatively favorable outcome. Nevertheless, epigenetic similarity with ATRT-MYC and the potential of malignant progression warrants close follow-up examinations. In line with recent developments of WHO nomenclature, we propose to refer to these tumors as “low-grade diffusely infiltrative tumor, SMARCB1-mutant”. |
format | Online Article Text |
id | pubmed-9165080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91650802022-06-05 ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC Thomas, Christian Federico, Aniello Bens, Susanne Hellström, Mats Casar-Borota, Olivera Kordes, Uwe Neumann, Julia E Dottermusch, Matthias Rodriguez, Fausto E Lo, Andrea C Cheng, Sylvia Hendson, Glenda Hukin, Juliette Hartmann, Christian Koch, Arend Capper, David Siebert, Reiner Paulus, Werner Nemes, Karolina Johann, Pascal D Frühwald, Michael C Kool, Marcel Hasselblatt, Martin Neuro Oncol Atypical Teratoid Rhabdoid Tumor Most atypical teratoid/rhabdoid tumors (ATRTs) occur in infants, but children and adolescents may also be affected. ATRTs occurring in older patients often comprise the molecular subgroup ATRT-MYC. Recently, central nervous system low-grade diffusely infiltrative tumor with INI1 deficiency (CNS LGDIT-INI1) has been described as a rare low-grade lesion (Nobusawa et al. Am J Surg Pathol 2020;44:1459-1468). Little is known on the molecular relationship of CNS LGDIT-INI1 and ATRT. We therefore further explored a series of six CNS LGDIT-INI1. The median age of the four males and two females was 16 years (range: 10-28 years). All tumors were of supratentorial location and showed low to moderate cellularity, diffuse growth of inconspicuous small SMARCB1-deficient tumor cells and reactive pleomorphic neuronal and glial cells with retained SMARCB1-staining in the background. In addition, two cases also displayed a high-grade rhabdoid component. After DNA isolation, purification and bisulfite conversion, samples were subjected to DNA methylation profiling (MethylationEPIC BeadChip array). Using DNA methylation-based classification and the Heidelberg Brain Tumor Classifier (version v11b4), all tumors were classified as ATRT-MYC (median calibrated score: 0.97). On t-SNE analysis, DNA methylation profiles grouped closely together in proximity to ATRT-MYC. Follow-up information was available for four cases (including the two cases with a high-grade component). Patients received heterogeneous treatments (including chemotherapy according to AT/RT protocols) and experienced stable disease or complete remission after an observation time of three to 56 months. In conclusion, CNS LGDIT-INI1 is a clinically and histologically distinct entity with relatively favorable outcome. Nevertheless, epigenetic similarity with ATRT-MYC and the potential of malignant progression warrants close follow-up examinations. In line with recent developments of WHO nomenclature, we propose to refer to these tumors as “low-grade diffusely infiltrative tumor, SMARCB1-mutant”. Oxford University Press 2022-06-03 /pmc/articles/PMC9165080/ http://dx.doi.org/10.1093/neuonc/noac079.006 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Atypical Teratoid Rhabdoid Tumor Thomas, Christian Federico, Aniello Bens, Susanne Hellström, Mats Casar-Borota, Olivera Kordes, Uwe Neumann, Julia E Dottermusch, Matthias Rodriguez, Fausto E Lo, Andrea C Cheng, Sylvia Hendson, Glenda Hukin, Juliette Hartmann, Christian Koch, Arend Capper, David Siebert, Reiner Paulus, Werner Nemes, Karolina Johann, Pascal D Frühwald, Michael C Kool, Marcel Hasselblatt, Martin ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC |
title | ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC |
title_full | ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC |
title_fullStr | ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC |
title_full_unstemmed | ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC |
title_short | ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC |
title_sort | atrt-07. low-grade diffusely infiltrative tumor, smarcb1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with atrt-myc |
topic | Atypical Teratoid Rhabdoid Tumor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165080/ http://dx.doi.org/10.1093/neuonc/noac079.006 |
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