Need Help?

Targetable NOTCH1 rearrangements in reninoma

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.

Request Access

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
EGAS00001005244 Other

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
EGAF00008080542 cram 17.9 GB
EGAF00008080543 cram 19.5 GB
EGAF00008080544 cram 16.9 GB
EGAF00008080545 cram 14.2 GB
EGAF00008080546 cram 13.4 GB
EGAF00008080547 cram 16.3 GB
EGAF00008080548 cram 14.4 GB
EGAF00008080549 cram 13.6 GB
8 Files (126.2 GB)