Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases

  1. Holdhof, Dörthe ORCID logo
  2. Johann, Pascal D.
  3. Spohn, Michael
  4. Bockmayr, Michael
  5. Safaei, Sepehr
  6. Joshi, Piyush
  7. Masliah-Planchon, Julien
  8. Ho, Ben
  9. Andrianteranagna, Mamy
  10. Bourdeaut, Franck
  11. Huang, Annie
  12. Kool, Marcel
  13. Upadhyaya, Santhosh A.
  14. Bendel, Anne E.
  15. Indenbirken, Daniela
  16. Foulkes, William D.
  17. Bush, Jonathan W.
  18. Creytens, David
  19. Kordes, Uwe
  20. Frühwald, Michael C.
  21. Hasselblatt, Martin
  22. Schüller, Ulrich ORCID logo

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1000 Titel
  • Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases
1000 Autor/in
  1. Holdhof, Dörthe |
  2. Johann, Pascal D. |
  3. Spohn, Michael |
  4. Bockmayr, Michael |
  5. Safaei, Sepehr |
  6. Joshi, Piyush |
  7. Masliah-Planchon, Julien |
  8. Ho, Ben |
  9. Andrianteranagna, Mamy |
  10. Bourdeaut, Franck |
  11. Huang, Annie |
  12. Kool, Marcel |
  13. Upadhyaya, Santhosh A. |
  14. Bendel, Anne E. |
  15. Indenbirken, Daniela |
  16. Foulkes, William D. |
  17. Bush, Jonathan W. |
  18. Creytens, David |
  19. Kordes, Uwe |
  20. Frühwald, Michael C. |
  21. Hasselblatt, Martin |
  22. Schüller, Ulrich |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-12-17
1000 Erschienen in
1000 Quellenangabe
  • 141(2):291-301
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-020-02250-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847432/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system. The underlying genetic cause are inactivating bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4. ATRT-SMARCA4 have been associated with a higher frequency of germline mutations, younger age, and an inferior prognosis in comparison to SMARCB1 mutated cases. Based on their DNA methylation profiles and transcriptomics, SMARCB1 mutated ATRTs have been divided into three distinct molecular subgroups: ATRT-TYR, ATRT-SHH, and ATRT-MYC. These subgroups differ in terms of age at diagnosis, tumor location, type of SMARCB1 alterations, and overall survival. ATRT-SMARCA4 are, however, less well understood, and it remains unknown, whether they belong to one of the described ATRT subgroups. Here, we examined 14 ATRT-SMARCA4 by global DNA methylation analyses. We show that they form a separate group segregating from SMARCB1 mutated ATRTs and from other SMARCA4-deficient tumors like small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) or SMARCA4 mutated extra-cranial malignant rhabdoid tumors. In contrast, medulloblastoma (MB) samples with heterozygous SMARCA4 mutations do not group separately, but with established MB subgroups. RNA sequencing of ATRT-SMARCA4 confirmed the clustering results based on DNA methylation profiling and displayed an absence of typical signature genes upregulated in SMARCB1 deleted ATRT. In summary, our results suggest that, in line with previous clinical observations, ATRT-SMARCA4 should be regarded as a distinct molecular subgroup.
1000 Sacherschließung
lokal Rhabdoid
lokal Transcription Factors/genetics [MeSH]
lokal Teratoma/pathology [MeSH]
lokal DNA Helicases/genetics [MeSH]
lokal Age of Onset [MeSH]
lokal SMARCA4
lokal Rhabdoid Tumor/pathology [MeSH]
lokal Central Nervous System Neoplasms/pathology [MeSH]
lokal DNA methylation
lokal Computational Biology [MeSH]
lokal Child [MeSH]
lokal Teratoma/genetics [MeSH]
lokal Mutation/genetics [MeSH]
lokal Adolescent [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal BRG1
lokal Survival Analysis [MeSH]
lokal Rhabdoid Tumor/genetics [MeSH]
lokal Middle Aged [MeSH]
lokal Nuclear Proteins/genetics [MeSH]
lokal Central Nervous System Neoplasms/genetics [MeSH]
lokal DNA Methylation [MeSH]
lokal Original Paper
lokal Young Adult [MeSH]
lokal RNA sequencing
lokal SMARCB1 Protein/genetics [MeSH]
lokal ATRT
lokal Gene Expression Profiling [MeSH]
lokal Child, Preschool [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-4664-3848|https://frl.publisso.de/adhoc/uri/Sm9oYW5uLCBQYXNjYWwgRC4=|https://frl.publisso.de/adhoc/uri/U3BvaG4sIE1pY2hhZWw=|https://frl.publisso.de/adhoc/uri/Qm9ja21heXIsIE1pY2hhZWw=|https://frl.publisso.de/adhoc/uri/U2FmYWVpLCBTZXBlaHI=|https://frl.publisso.de/adhoc/uri/Sm9zaGksIFBpeXVzaA==|https://frl.publisso.de/adhoc/uri/TWFzbGlhaC1QbGFuY2hvbiwgSnVsaWVu|https://frl.publisso.de/adhoc/uri/SG8sIEJlbg==|https://frl.publisso.de/adhoc/uri/QW5kcmlhbnRlcmFuYWduYSwgTWFteQ==|https://frl.publisso.de/adhoc/uri/Qm91cmRlYXV0LCBGcmFuY2s=|https://frl.publisso.de/adhoc/uri/SHVhbmcsIEFubmll|https://frl.publisso.de/adhoc/uri/S29vbCwgTWFyY2Vs|https://frl.publisso.de/adhoc/uri/VXBhZGh5YXlhLCBTYW50aG9zaCBBLg==|https://frl.publisso.de/adhoc/uri/QmVuZGVsLCBBbm5lIEUu|https://frl.publisso.de/adhoc/uri/SW5kZW5iaXJrZW4sIERhbmllbGE=|https://frl.publisso.de/adhoc/uri/Rm91bGtlcywgV2lsbGlhbSBELg==|https://frl.publisso.de/adhoc/uri/QnVzaCwgSm9uYXRoYW4gVy4=|https://frl.publisso.de/adhoc/uri/Q3JleXRlbnMsIERhdmlk|https://frl.publisso.de/adhoc/uri/S29yZGVzLCBVd2U=|https://frl.publisso.de/adhoc/uri/RnLDvGh3YWxkLCBNaWNoYWVsIEMu|https://frl.publisso.de/adhoc/uri/SGFzc2VsYmxhdHQsIE1hcnRpbg==|https://orcid.org/0000-0002-8731-1121
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1000 Erstellt am 2023-11-17T00:01:37.731+0100
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1000 Zuletzt bearbeitet 2023-12-01T04:25:30.155+0100
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