Evidence map›Paper›PMID 40481679›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025

Wilms tumor characteristics in children with heterozygous germline DIS3L2 variants.

S E van Peer, T D Treger, J Wegert, J A Hol, J Le Gall, E E Jakkula, J Kamihara, E A Mullen, N Graf, S Behjati and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

25 authors.

S E van PeerPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. Electronic address: s.e.vanpeer-3@prinsesmaximacentrum.nl.
T D TregerWellcome Sanger Institute, Hinxton, United Kingdom; Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
J WegertTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Wuerzburg University, Wuerzburg, Germany.
J A HolPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
J Le GallDepartment of Genetics, Institut Curie, Paris, France.
E E JakkulaDepartment of Clinical Genetics, HUSLAB, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
J KamiharaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA.
E A MullenDepartment of Pediatric Oncology, Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA.
N GrafDepartment of Paediatric Oncology and Hematology, Saarland University Hospital, Homburg, Germany.
S BehjatiWellcome Sanger Institute, Hinxton, United Kingdom; Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
R Al-SaadiDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom; Department of Histopathology, Great Ormond Street Hospital for Children, London, United Kingdom.
C DuncanGreat Ormond Street Hospital for Children (GOSH), NHS Foundation Trust, London, United Kingdom.
J SchiendaDepartment of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA.
R de PutterCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
J BrzezinskiDivision of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
A VerschuurPediatric Oncology and Hematology Department, La Timone, Hospital, AP-HM, Marseille, France.
O MichaeliDepartment of Pediatric Hematology and Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
M V OrtizDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
J C HerkertDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
R ArmstrongDepartments of Medical Genetics, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom.
E WaandersDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
R P KuiperPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
M M van den Heuvel-EibrinkPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Division of Child Health, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
M GesslerTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Wuerzburg University, Wuerzburg, Germany; Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany.
M C J JongmansPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748Wellcome Trust 108413/A/15/D
6 · The paper itself

Abstract

purposeHeterozygous germline DIS3L2 pathogenic variants were recently linked to Wilms tumor (WT) predisposition. Limited data on cancer penetrance and characteristics complicate surveillance/management recommendations. This study aims to describe an extended cohort of children with WTs and heterozygous germline DIS3L2 (likely) pathogenic variants ([L]PVs).

methodsClinical and tumor data of children with WT and heterozygous germline DIS3L2 (L)PVs were retrospectively collected.

resultsThirty-four children were identified, including 4 familial cases. Germline (L)PVs included exon 9 deletions (n = 28) and other (n = 6) (L)PVs. Seventeen parents were confirmed to have the DIS3L2 (L)PV, of whom 1 had a past WT. Median age at WT diagnosis was 41 months (range: 8-101). A somatic second hit in DIS3L2 was found in 19 of 20 children with genetic tumor data. Five children had bilateral WTs and 11 had metastases (32%). Eight children had high-risk tumor histology (24%, of which 7 post-chemotherapy blastemal). Three children relapsed or developed a second primary tumor; 4 children were deceased. Recurring clinical features were lacking.

conclusionChildren with WTs and heterozygous germline DIS3L2 (L)PVs lack a recognizable phenotype. DIS3L2 (L)PVs are a cause for familial WT, but WT penetrance is likely low. This cohort exhibits a high percentage of metastases and high-risk blastemal tumors, which need further study.

Indexed as

ExoribonucleasesKidney NeoplasmsWilms TumorChildChild, PreschoolFemaleGerm-Line MutationHeterozygoteHumansInfantKidneyMaleDIS3L2 protein, humanExoribonucleasesCancer predispositionDIS3L2NephroblastomaPediatricWilms tumor

Identifiers

PMID40481679
PMCPMC13158626

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.