Evidence map›Paper›PMID 37749094›Full record

ArticleNature communications2023

Targetable NOTCH1 rearrangements in reninoma.

Taryn D Treger, John E G Lawrence, Nathaniel D Anderson, Tim H H Coorens, Aleksandra Letunovska, Emilie Abby, Henry Lee-Six, Thomas R W Oliver, Reem Al-Saadi, Kjell Tullus and 11 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. The genetics of hypertension.Nature reviews. Nephrology · 2026
    Review
  2. Article
  3. Article
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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

21 authors at 6 institutions in 2 countries.

Taryn D Treger *Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
John E G Lawrence *Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Nathaniel D AndersonWellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Tim H H CoorensBroad Institute of MIT and Harvard, Cambridge, 02142 MA, USA.ORCID http://orcid.org/0000-0002-5826-3554
Aleksandra LetunovskaUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Emilie AbbyWellcome Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0003-0284-4760
Henry Lee-SixWellcome Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0003-4831-8088
Thomas R W OliverWellcome Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0003-4306-0102
Reem Al-SaadiUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.ORCID http://orcid.org/0000-0002-0816-5649
Kjell TullusUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Guillaume MorcretteUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
J Ciaran HutchinsonNIHR Great Ormond Street Hospital Biomedical Research Centre, London, WC1N 3JH, UK.
Dyanne RamplingNIHR Great Ormond Street Hospital Biomedical Research Centre, London, WC1N 3JH, UK.
Neil SebireUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Kathy Pritchard-JonesUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Matthew D YoungWellcome Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0003-0937-5290
Thomas J MitchellWellcome Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0003-0761-9503
Philip H JonesWellcome Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0002-5904-795X
Maxine TranSpecialist Centre for Kidney Cancer, Royal Free Hospital, London, NW3 2QG, UK. m.tran@ucl.ac.uk.
Sam BehjatiWellcome Sanger Institute, Hinxton, CB10 1SA, UK. sb31@sanger.ac.uk.ORCID http://orcid.org/0000-0002-6600-7665
Tanzina ChowdhuryUCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK. Tanzina.Chowdhury@gosh.nhs.uk.
Great Ormond Street Hospital · GBUniversity of Cambridge · GBCambridge University Hospitals NHS Foundation Trust · GBWellcome Sanger Institute · GBBroad Institute · USThe Royal Free Hospital · GB

Funding

Cancer Research UK 17297Cancer Research UK C609/A27326Wellcome Trust 108413/A/15/DWellcome Trust 223135/Z/21/ZWellcome Trust 296194
6 · The paper itself

Abstract

Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma.

Indexed as

Kidney NeoplasmsReninHumansJuxtaglomerular ApparatusKidney GlomerulusReceptor, Notch1Signal TransductionNOTCH1 protein, humanReceptor, Notch1Renin

Identifiers

PMID37749094
PMCPMC10519988
OpenAlexW4387019590

What OpenQuestion holds

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LicenceCC BY
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.