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Targetable NOTCH1 rearrangements in reninoma - WGS

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 assessed somatic changes in reninoma and found structural variants that generate canonical activating rearrangements of NOTCH1, whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observed 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.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001004237 Cancer Genomics
EGAS00001006486 Whole Genome Sequencing

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00008075562 cram 30.6 GB
EGAF00008075563 cram 44.9 GB
EGAF00008075564 cram 20.7 GB
EGAF00008075565 cram 18.7 GB
EGAF00008075566 cram 7.6 GB
EGAF00008075567 cram 11.6 GB
EGAF00008075568 cram 5.1 GB
EGAF00008075569 cram 4.7 GB
EGAF00008075570 cram 5.1 GB
EGAF00008075571 cram 4.7 GB
EGAF00008075572 cram 5.1 GB
EGAF00008075573 cram 4.7 GB
EGAF00008078348 cram 72.5 GB
EGAF00008078349 cram 75.1 GB
EGAF00008078350 cram 71.0 GB
15 Files (382.1 GB)