Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression

  1. Apps, John ORCID logo
  2. Gonzalez-Meljem, Jose Mario
  3. Guiho, Romain
  4. Pickles, Jessica C.
  5. Prince, Eric
  6. Schwalbe, Edward
  7. Joshi, Nikhil
  8. Stone, Thomas J.
  9. Ogunbiyi, Olumide
  10. Chalker, Jane
  11. Bassey, Akang
  12. Otto, Georg
  13. Davies, Rosalind
  14. Hughes, Debbie
  15. Brandner, Sebastian
  16. Tan, Enrica
  17. Lee, Victoria
  18. Hayhurst, Caroline
  19. Kline, Cassie
  20. Castellano, Sergi
  21. Hankinson, Todd
  22. Deutschbein, Timo
  23. Jacques, Thomas S.
  24. Martinez-Barbera, Juan Pedro

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1000 Titel
  • Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression
1000 Autor/in
  1. Apps, John |
  2. Gonzalez-Meljem, Jose Mario |
  3. Guiho, Romain |
  4. Pickles, Jessica C. |
  5. Prince, Eric |
  6. Schwalbe, Edward |
  7. Joshi, Nikhil |
  8. Stone, Thomas J. |
  9. Ogunbiyi, Olumide |
  10. Chalker, Jane |
  11. Bassey, Akang |
  12. Otto, Georg |
  13. Davies, Rosalind |
  14. Hughes, Debbie |
  15. Brandner, Sebastian |
  16. Tan, Enrica |
  17. Lee, Victoria |
  18. Hayhurst, Caroline |
  19. Kline, Cassie |
  20. Castellano, Sergi |
  21. Hankinson, Todd |
  22. Deutschbein, Timo |
  23. Jacques, Thomas S. |
  24. Martinez-Barbera, Juan Pedro |
1000 Verlag BioMed Central
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-08-10
1000 Erschienen in
1000 Quellenangabe
  • 12(1):127
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s40478-024-01838-4 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316312/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:p>The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show the presence of copy number alterations and clonal evolution across recurrence in 6 cases of ACP, and analysis of additional whole genome sequencing data from the Children’s Brain Tumour Network confirms chromosomal arm copy number changes in at least 7/67 ACP cases. The activation of the MAPK/ERK pathway, a feature previously shown in primary ACP, is observed in all but one recurrent cases of ACP. The only ACP without MAPK activation is an aggressive case of recurrent malignant human craniopharyngioma harbouring a <jats:italic>CTNNB1</jats:italic> mutation and loss of <jats:italic>TP53</jats:italic>. Providing support for a functional role of this <jats:italic>TP53</jats:italic> mutation, we show that <jats:italic>Trp53</jats:italic> loss in a murine model of ACP results in aggressive tumours and reduced mouse survival. Finally, we characterise the tumour immune infiltrate showing differences in the cellular composition and spatial distribution between ACP and PCP. Together, these analyses have revealed novel insights into recurrent craniopharyngioma and provided preclinical evidence supporting the evaluation of MAPK pathway inhibitors and immunomodulatory approaches in clinical trials in against recurrent ACP.</jats:p>
1000 Sacherschließung
lokal Disease Progression [MeSH]
lokal Macrophage/microglia
lokal Pituitary Neoplasms/metabolism [MeSH]
lokal MEK inhibitor
lokal Pituitary Neoplasms/pathology [MeSH]
lokal Tumor Suppressor Protein p53/metabolism [MeSH]
lokal Neoplasm Recurrence, Local/pathology [MeSH]
lokal beta Catenin/genetics [MeSH]
lokal Male [MeSH]
lokal MAP Kinase Signaling System/physiology [MeSH]
lokal Neoplasm Recurrence, Local/genetics [MeSH]
lokal Craniopharyngioma/genetics [MeSH]
lokal Female [MeSH]
lokal beta Catenin/metabolism [MeSH]
lokal Clonal Evolution/genetics [MeSH]
lokal Craniopharyngioma/pathology [MeSH]
lokal Craniopharyngioma
lokal Humans [MeSH]
lokal MAPK signalling pathway
lokal Pituitary Neoplasms/genetics [MeSH]
lokal Animals [MeSH]
lokal Tumor Suppressor Protein p53/genetics [MeSH]
lokal Mice [MeSH]
lokal MAP Kinase Signaling System/genetics [MeSH]
lokal Craniopharyngioma/metabolism [MeSH]
lokal Research
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-7902-482X|https://frl.publisso.de/adhoc/uri/R29uemFsZXotTWVsamVtLCBKb3NlIE1hcmlv|https://frl.publisso.de/adhoc/uri/R3VpaG8sIFJvbWFpbg==|https://frl.publisso.de/adhoc/uri/UGlja2xlcywgSmVzc2ljYSBDLg==|https://frl.publisso.de/adhoc/uri/UHJpbmNlLCBFcmlj|https://frl.publisso.de/adhoc/uri/U2Nod2FsYmUsIEVkd2FyZA==|https://frl.publisso.de/adhoc/uri/Sm9zaGksIE5pa2hpbA==|https://frl.publisso.de/adhoc/uri/U3RvbmUsIFRob21hcyBKLg==|https://frl.publisso.de/adhoc/uri/T2d1bmJpeWksIE9sdW1pZGU=|https://frl.publisso.de/adhoc/uri/Q2hhbGtlciwgSmFuZQ==|https://frl.publisso.de/adhoc/uri/QmFzc2V5LCBBa2FuZw==|https://frl.publisso.de/adhoc/uri/T3R0bywgR2Vvcmc=|https://frl.publisso.de/adhoc/uri/RGF2aWVzLCBSb3NhbGluZA==|https://frl.publisso.de/adhoc/uri/SHVnaGVzLCBEZWJiaWU=|https://frl.publisso.de/adhoc/uri/QnJhbmRuZXIsIFNlYmFzdGlhbg==|https://frl.publisso.de/adhoc/uri/VGFuLCBFbnJpY2E=|https://frl.publisso.de/adhoc/uri/TGVlLCBWaWN0b3JpYQ==|https://frl.publisso.de/adhoc/uri/SGF5aHVyc3QsIENhcm9saW5l|https://frl.publisso.de/adhoc/uri/S2xpbmUsIENhc3NpZQ==|https://frl.publisso.de/adhoc/uri/Q2FzdGVsbGFubywgU2VyZ2k=|https://frl.publisso.de/adhoc/uri/SGFua2luc29uLCBUb2Rk|https://frl.publisso.de/adhoc/uri/RGV1dHNjaGJlaW4sIFRpbW8=|https://frl.publisso.de/adhoc/uri/SmFjcXVlcywgVGhvbWFzIFMu|https://frl.publisso.de/adhoc/uri/TWFydGluZXotQmFyYmVyYSwgSnVhbiBQZWRybw==
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  • DeepGreen-ID: 8b2de5f6eaa643db83e7c6ca08bb455f ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Förderer
  1. CHILDREN with CANCER UK |
  2. Cancer Research UK |
  3. Children's Cancer and Leukaemia Group |
  4. Brain Tumour Charity |
1000 Fördernummer
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  4. -
1000 Förderprogramm
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1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer CHILDREN with CANCER UK |
    1000 Förderprogramm -
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Cancer Research UK |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Children's Cancer and Leukaemia Group |
    1000 Förderprogramm -
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer Brain Tumour Charity |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
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1000 @id frl:6492184.rdf
1000 Erstellt am 2025-02-03T16:56:48.463+0100
1000 Erstellt von 322
1000 beschreibt frl:6492184
1000 Zuletzt bearbeitet 2025-09-12T12:36:00.799+0200
1000 Objekt bearb. Fri Sep 12 12:36:00 CEST 2025
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  1. oai:frl.publisso.de:frl:6492184 |
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