Evidence map›Paper›PMID 39127699›Full record

ArticleActa neuropathologica communications2024

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

John R Apps, Jose Mario Gonzalez-Meljem, Romain Guiho, Jessica C Pickles, Eric Prince, Edward Schwalbe, Nikhil Joshi, Thomas J Stone, Olumide Ogunbiyi, Jane Chalker and 14 more

Abstract read
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In one paragraph

Article in Acta neuropathologica communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

John R AppsInstitute of Cancer and Genomic Sciences, Edgbaston Campus, University of Birmingham, Birmingham, B15 2TT, UK. j.r.apps@bham.ac.uk.ORCID 0000-0001-7902-482X
Jose Mario Gonzalez-MeljemDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Romain GuihoDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Jessica C PicklesDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Eric PrinceDepartments of Neurosurgery and Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, USA.
Edward SchwalbeDepartment of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Nikhil JoshiDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, USA.
Thomas J StoneDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Olumide OgunbiyiDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Jane ChalkerGreat Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
Akang BasseyDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Georg OttoDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Rosalind DaviesDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Debbie HughesInstitute of Cancer Research, Sutton, UK.
Sebastian BrandnerDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Enrica TanKK Women's and Children's Hospital, Singapore, Singapore.
Victoria LeeSheffield Children's Hospital NHS Foundation Trust, Sheffield, UK.
Caroline HayhurstUniversity Hospital of Wales, Cardiff, UK.
Cassie KlineDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, USA.
Sergi CastellanoDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Todd HankinsonDepartments of Neurosurgery and Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, USA.
Timo DeutschbeinDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
Thomas S JacquesDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Juan Pedro Martinez-BarberaDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.

Funding

Computational Bioscience Program Training GrantT15LM009451 · NLM · UNIVERSITY OF COLORADO DENVER · PI Katherina Kechris-Mays, Arjun Krishnan · 2007 to 2026
$11.7M
Brain Tumour Charity GN-000382Brain Tumour Charity GN-000522Cancer Research UK C54322/A27727Cancer Research UK DRCRPG-NOV22/100002Children's Cancer and Leukaemia Group 2017-05CHILDREN with CANCER UK 15-190NLM NIH HHS T15 LM009451
6 · The paper itself

Abstract

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 CTNNB1 mutation and loss of TP53. Providing support for a functional role of this TP53 mutation, we show that Trp53 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.

Indexed as

Clonal EvolutionCraniopharyngiomaMAP Kinase Signaling SystemNeoplasm Recurrence, LocalPituitary NeoplasmsTumor Suppressor Protein p53Animalsbeta CateninDisease ProgressionFemaleHumansMaleMicebeta CateninCTNNB1 protein, humanTP53 protein, humanTumor Suppressor Protein p53CraniopharyngiomaMacrophage/microgliaMAPK signalling pathwayMEK inhibitor

Identifiers

PMID39127699
PMCPMC11316312

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.