Genetic and epigenetic characterization of posterior pituitary tumors

  1. Schmid, Simone ORCID logo
  2. Solomon, David ORCID logo
  3. Perez, Eilis
  4. Thieme, Anne
  5. Kleinschmidt-DeMasters, Bette K.
  6. Giannini, Caterina
  7. Reinhardt, Annekathrin
  8. Asa, Sylvia L.
  9. Mete, Ozgur
  10. Stichel, Damian
  11. Siewert, Christin
  12. Dittmayer, Carsten
  13. Hasselblatt, Martin
  14. Paulus, Werner
  15. Nagel, Christoph
  16. Harter, Patrick N.
  17. Schittenhelm, Jens
  18. Honegger, Jürgen
  19. Rushing, Elisabeth
  20. Coras, Roland
  21. Pfister, Stefan M.
  22. Buslei, Rolf
  23. Koch, Arend
  24. Perry, Arie
  25. Jones, David T. W.
  26. von Deimling, Andreas
  27. Capper, David ORCID logo
  28. Lopes, Maria Beatriz ORCID logo

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1000 Titel
  • Genetic and epigenetic characterization of posterior pituitary tumors
1000 Autor/in
  1. Schmid, Simone |
  2. Solomon, David |
  3. Perez, Eilis |
  4. Thieme, Anne |
  5. Kleinschmidt-DeMasters, Bette K. |
  6. Giannini, Caterina |
  7. Reinhardt, Annekathrin |
  8. Asa, Sylvia L. |
  9. Mete, Ozgur |
  10. Stichel, Damian |
  11. Siewert, Christin |
  12. Dittmayer, Carsten |
  13. Hasselblatt, Martin |
  14. Paulus, Werner |
  15. Nagel, Christoph |
  16. Harter, Patrick N. |
  17. Schittenhelm, Jens |
  18. Honegger, Jürgen |
  19. Rushing, Elisabeth |
  20. Coras, Roland |
  21. Pfister, Stefan M. |
  22. Buslei, Rolf |
  23. Koch, Arend |
  24. Perry, Arie |
  25. Jones, David T. W. |
  26. von Deimling, Andreas |
  27. Capper, David |
  28. Lopes, Maria Beatriz |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-10-18
1000 Erschienen in
1000 Quellenangabe
  • 142(6):1025-1043
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-021-02377-1 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568760/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.
1000 Sacherschließung
lokal Epigenesis, Genetic [MeSH]
lokal Brain tumor
lokal Adenoma, Oxyphilic/genetics [MeSH]
lokal Granular Cell Tumor/genetics [MeSH]
lokal Humans [MeSH]
lokal Original Paper
lokal Spindle cell oncocytoma
lokal Granular cell tumor
lokal Pituitary Neoplasms/genetics [MeSH]
lokal Posterior pituitary gland neoplasms
lokal Pituicytoma
lokal Molecular neuropathology
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-5787-7343|https://orcid.org/0000-0003-4571-7999|https://frl.publisso.de/adhoc/uri/UGVyZXosIEVpbGlz|https://frl.publisso.de/adhoc/uri/VGhpZW1lLCBBbm5l|https://frl.publisso.de/adhoc/uri/S2xlaW5zY2htaWR0LURlTWFzdGVycywgQmV0dGUgSy4=|https://frl.publisso.de/adhoc/uri/R2lhbm5pbmksIENhdGVyaW5h|https://frl.publisso.de/adhoc/uri/UmVpbmhhcmR0LCBBbm5la2F0aHJpbg==|https://frl.publisso.de/adhoc/uri/QXNhLCBTeWx2aWEgTC4=|https://frl.publisso.de/adhoc/uri/TWV0ZSwgT3pndXI=|https://frl.publisso.de/adhoc/uri/U3RpY2hlbCwgRGFtaWFu|https://frl.publisso.de/adhoc/uri/U2lld2VydCwgQ2hyaXN0aW4=|https://frl.publisso.de/adhoc/uri/RGl0dG1heWVyLCBDYXJzdGVu|https://frl.publisso.de/adhoc/uri/SGFzc2VsYmxhdHQsIE1hcnRpbg==|https://frl.publisso.de/adhoc/uri/UGF1bHVzLCBXZXJuZXI=|https://frl.publisso.de/adhoc/uri/TmFnZWwsIENocmlzdG9waA==|https://frl.publisso.de/adhoc/uri/SGFydGVyLCBQYXRyaWNrIE4u|https://frl.publisso.de/adhoc/uri/U2NoaXR0ZW5oZWxtLCBKZW5z|https://frl.publisso.de/adhoc/uri/SG9uZWdnZXIsIErDvHJnZW4=|https://frl.publisso.de/adhoc/uri/UnVzaGluZywgRWxpc2FiZXRo|https://frl.publisso.de/adhoc/uri/Q29yYXMsIFJvbGFuZA==|https://frl.publisso.de/adhoc/uri/UGZpc3RlciwgU3RlZmFuIE0u|https://frl.publisso.de/adhoc/uri/QnVzbGVpLCBSb2xm|https://frl.publisso.de/adhoc/uri/S29jaCwgQXJlbmQ=|https://frl.publisso.de/adhoc/uri/UGVycnksIEFyaWU=|https://frl.publisso.de/adhoc/uri/Sm9uZXMsIERhdmlkIFQuIFcu|https://frl.publisso.de/adhoc/uri/dm9uIERlaW1saW5nLCBBbmRyZWFz|https://orcid.org/0000-0003-1945-497X|https://orcid.org/0000-0001-8661-6727
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  1. Genetic and epigenetic characterization of posterior pituitary tumors
    Genetic and epigenetic characterization of posterior pituitary tumors
1000 Objektart article
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1000 Erstellt am 2023-05-11T10:25:05.764+0200
1000 Erstellt von 322
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1000 Zuletzt bearbeitet 2023-10-20T09:11:59.452+0200
1000 Objekt bearb. Fri Oct 20 09:11:59 CEST 2023
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