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Updated: Jul 15, 2025
08:21
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
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Targetable NOTCH1 rearrangements in reninoma
Taryn D Treger1,2,3, John E G Lawrence1,3, Nathaniel D Anderson1
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Nature Communications
|September 25, 2023
Summary
Reninomas, rare kidney tumors, exhibit NOTCH1 gene rearrangements that activate signaling pathways. These findings suggest a new therapeutic target for renin-secreting tumors.
Area of Science:
- Oncology
- Genetics
- Nephrology
Background:
- Reninomas are rare, renin-secreting kidney tumors originating from juxtaglomerular cells.
- These cells are part of the juxtaglomerular apparatus, crucial for regulating blood pressure via renin secretion.
Purpose of the Study:
- To investigate somatic genetic alterations in reninomas.
- To identify molecular mechanisms driving reninoma development and potential therapeutic targets.
Main Methods:
- Analysis of somatic genetic changes in reninoma tissue.
- Assessment of gene expression for NOTCH1, NRARP, and renin.
- Re-analysis of published reninoma bulk transcriptome data.
Main Results:
- Discovery of structural variants in reninoma leading to NOTCH1 activation and NRARP downregulation.
- Observation of excessive renin and NOTCH1 signaling mRNA in single reninoma nuclei.
- Confirmation of dysregulated Notch pathway signaling in reninoma through transcriptome re-analysis.
Conclusions:
- NOTCH1 gene rearrangements are identified in reninomas.
- Dysregulated Notch signaling is a potential disease-defining feature of reninoma.
- NOTCH1 inhibitors represent a potential therapeutic strategy for reninomas.
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