Evidence map›Paper›PMID 41215730›Full record

ArticleDisease models & mechanisms2026

Impaired nuclear PTEN function drives macrocephaly, lymphadenopathy and late-onset cancer in PTEN hamartoma tumour syndrome.

Priyanka Tibarewal, Victoria Rathbone, Sarah E Conduit, Gala Anastasia Electra Classen, Fiona Black, Mohammad Amin Danesh, Georgia Constantinou, Zeinab Asgarian, Koujiro Tohyama, Nisha Kriplani and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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

32 authors.

Priyanka TibarewalCancer Institute, University College London, London WC1E 6BT, UK.ORCID 0000-0003-3510-8428
Victoria RathboneCancer Institute, University College London, London WC1E 6BT, UK.
Sarah E ConduitCancer Institute, University College London, London WC1E 6BT, UK.
Gala Anastasia Electra ClassenCancer Institute, University College London, London WC1E 6BT, UK.
Fiona BlackCancer Institute, University College London, London WC1E 6BT, UK.
Mohammad Amin DaneshCancer Institute, University College London, London WC1E 6BT, UK.ORCID 0009-0002-8580-6793
Georgia ConstantinouCancer Institute, University College London, London WC1E 6BT, UK.
Zeinab AsgarianWolfson Institute of Biomedical Research, University College London, London WC1E 6BT, UK.
Koujiro TohyamaDepartment of Physiology, School of Dentistry, Iwate Medical University, Yahaba 028-3694, Japan.
Nisha KriplaniInstitute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, UK.
Virginia Alvarez GarciaInstitute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, UK.
Elizabeth FoxallCancer Institute, University College London, London WC1E 6BT, UK.
Djenat BelarbiUniversité Paris Cité, 75014 Paris, France.
Marie LeverveUniversité Paris Cité, 75014 Paris, France.
Wayne PearceCancer Institute, University College London, London WC1E 6BT, UK.ORCID 0000-0001-5407-4767
Mahreen AdilCancer Institute, University College London, London WC1E 6BT, UK.
Zofia VaryovaCancer Institute, University College London, London WC1E 6BT, UK.
Lucia CondeCancer Institute, University College London, London WC1E 6BT, UK.
Adriana AlvesCancer Institute, University College London, London WC1E 6BT, UK.
Glenn R MassonMRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Roger L WilliamsMRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Adrienne M FlanaganResearch Department of Pathology, University College London, London WC1E 6DE, UK.
Javier HerreroCancer Institute, University College London, London WC1E 6BT, UK.
Isra Ahmed MohamedWolfson Diabetes and Endocrine Clinic, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Katerina StroudDepartment of Genomic Medicine, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge CB2 0QQ, Cambridge, UK.
Marc TischkowitzDepartment of Genomic Medicine, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge CB2 0QQ, Cambridge, UK.
Katherine LachlanWessex Clinical Genetics Service, University Hospital Southampton, Princess Anne Hospital, Southampton SO16 5YA, UK.
Cheryl L ScudamoreExepathology, Exmouth, UK.ORCID 0000-0002-7101-1714
Mark G H ScottUniversité Paris Cité, 75014 Paris, France.
Nicholas R LeslieInstitute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, UK.
Nicoletta KessarisWolfson Institute of Biomedical Research, University College London, London WC1E 6BT, UK.ORCID 0000-0003-1191-6009
Bart VanhaesebroeckCancer Institute, University College London, London WC1E 6BT, UK.ORCID 0000-0002-7074-3673

Funding

Biotechnology and Biological Sciences Research Council BB/N009061/1Biotechnology and Biological Sciences Research Council BB/W007460/1Cancer Research UK C23338/A25722Cancer Research UK C416/A25145Cancer Research UK C416/A29287Cancer Research UK CANTAC721\100022European Commission H2020-MSCA-IF-2018 GA: 838559Fondation ARC pour la recherche sur le cancer ARCPJA2022060005118Fondation ARC pour la Recherche sur le Cancer ARCPJA2022060005118Jean Shanks FoundationJean Shanks Foundation Clinical PhD studentshipLigue Contre le CancerLigue Contre le Cancer NAMedical Research Council MC-A024-5PF91NIHR Cambridge Biomedical Research Centre NIHR203312PTEN Research UCL-16-001PTEN Research UCL-20-001PTEN Research UOC-17-001University College LondonWellcome TrustWellcome Trust 108726/Z/15/Z
6 · The paper itself

Abstract

PTEN hamartoma tumour syndrome (PHTS), a rare disease caused by germline heterozygous PTEN variants, is associated with multi-organ/tissue overgrowth, autism spectrum disorder and increased cancer risk. Phenotypic variability in PHTS is partly due to diverse PTEN variants and the protein's multifaceted functions. PTEN is primarily a phosphatidylinositol(3,4,5)trisphosphate (PIP3) phosphatase regulating PI3K/AKT signalling but also maintains chromosomal stability through nuclear functions such as double-stranded (ds)DNA damage repair. Here, we show that PTEN-R173C, a pathogenic variant frequently found in PHTS and somatic cancer, has elevated PIP3 phosphatase activity that effectively regulates canonical PI3K/AKT signalling. However, PTEN-R173C is unstable and excluded from the nucleus. We generated Pten+/R173C mice which developed few tumours during their lifetime, aligning with normal PI3K/AKT signalling. However, they exhibited lymphoid hyperplasia, macrocephaly and brain abnormalities, associated with impaired nuclear functions of PTEN-R173C, demonstrated by reduced dsDNA damage repair. We integrated PHTS patient data with our mouse model results, and propose that defective nuclear functions of PTEN variants can predict the onset of PHTS phenotypes and that late-onset cancer in these individuals may arise from secondary genetic alterations, facilitated by compromised dsDNA repair.

Indexed as

Cell NucleusHamartoma Syndrome, MultipleMegalencephalyNeoplasmsPTEN PhosphohydrolaseAge of OnsetAnimalsDisease Models, AnimalDNA RepairHumansMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanPten protein, mouseASDCancerMacrocephalyPHTSPI3KPTEN

Identifiers

PMID41215730
PMCPMC12817337

What Socratic holds

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Registered trials

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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 Socratic graph.