The_Little_Princess_Knowledge_Bank_

We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001009812	Cancers of adults typically arise through progressive rounds of clonal diversification and intratumoral selective sweeps which generate a long mutational trunk with shorter subclonal branches. Here, we investigated whether tumors of young children exhibit the same phylogenetic configuration. We studied three infants, including two newborns, with the childhood kidney cancer, Wilms tumour, through whole genome sequencing of bulk tissues, of single cell derived organoids, and of microdissections. All three cancers exhibited unusual driver events, with tumours of newborns harbouring FOXR2 rearrangements, delineating a distinct variant of Wilms tumour. Phylogenetic analyses suggest that tumors were seeded in an early, possibly confined window of development. Unusually, following seeding there was extensive polyclonal diversification with little evidence of clonal sweeps, leading to a distinct phylogenetic configuration more reminiscent of normal tissues rather than of adult cancers. These findings indicate that some childhood cancers may diversify via unorthodox phylogenetic pathways.	HiSeq X Ten Illumina NovaSeq 6000	-
EGAD00001010888	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.	Illumina NovaSeq 6000	3
EGAD00001015406	A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resolution, high depth sequencing approaches. We found that apparent hypomutation was the result of unusual clonal architecture due to a normal tissue-like mode of tumour evolution, raising the possibility that the mutation burden of some cancers has been systematically misjudged.	HiSeq X Ten Illumina NovaSeq 6000	-

Publications	Citations
Targetable NOTCH1 rearrangements in reninoma. Treger TD, Lawrence JEG, Anderson ND, Coorens THH, Letunovska A, Abby E, Lee-Six H, Oliver TRW, Al-Saadi R, Tullus K, Morcrette G, Hutchinson JC, Rampling D, Sebire N, Pritchard-Jones K, Young MD, Mitchell TJ, Jones PH, Tran M, Behjati S, Chowdhury T. Nat Commun 14: 2023 5826	1
Predisposition footprints in the somatic genome of Wilms tumours. Treger TD, Wegert J, Wenger A, Coorens THH, Al-Saadi R, Kemps PG, Kennedy J, Parks C, Anderson ND, Hodder A, Letunovska A, Jung H, Ogbonnah T, Trinh MK, Lee-Six H, Morcrette G, van den Heuvel-Eibrink MM, Drost J, van Boxtel R, Bertrums EJM, Goemans BF, Antoniou E, Reinhardt D, Streitenberger H, Ziegler B, Bartram J, Hutchinson JC, Vujanic GM, Vokuhl C, Chowdhury T, Furtwängler R, Graf N, Pritchard-Jones K, Gessler M, Behjati S. Cancer Discov 15: 2025 286-298	0

Publications

Citations

Targetable NOTCH1 rearrangements in reninoma.
Treger TD, Lawrence JEG, Anderson ND, Coorens THH, Letunovska A, Abby E, Lee-Six H, Oliver TRW, Al-Saadi R, Tullus K, Morcrette G, Hutchinson JC, Rampling D, Sebire N, Pritchard-Jones K, Young MD, Mitchell TJ, Jones PH, Tran M, Behjati S, Chowdhury T. Nat Commun 14: 2023 5826

Predisposition footprints in the somatic genome of Wilms tumours.
Treger TD, Wegert J, Wenger A, Coorens THH, Al-Saadi R, Kemps PG, Kennedy J, Parks C, Anderson ND, Hodder A, Letunovska A, Jung H, Ogbonnah T, Trinh MK, Lee-Six H, Morcrette G, van den Heuvel-Eibrink MM, Drost J, van Boxtel R, Bertrums EJM, Goemans BF, Antoniou E, Reinhardt D, Streitenberger H, Ziegler B, Bartram J, Hutchinson JC, Vujanic GM, Vokuhl C, Chowdhury T, Furtwängler R, Graf N, Pritchard-Jones K, Gessler M, Behjati S. Cancer Discov 15: 2025 286-298