Treger, Taryn D;
Wegert, Jenny;
Wenger, Anna;
Coorens, Tim HH;
Al-Saadi, Reem;
Kemps, Paul G;
Kennedy, Jonathan;
... Behjati, Sam; + view all
(2024)
Predisposition footprints in the somatic genome of Wilms tumours.
Cancer Discovery
10.1158/2159-8290.CD-24-0878.
(In press).
![[thumbnail of EMS202070.pdf]](https://discovery-pp.ucl.ac.uk/style/images/fileicons/text.png) |
Text
EMS202070.pdf - Accepted Version Access restricted to UCL open access staff until 13 December 2025. Download (1MB) |
|
Text (Supplementary Figures 1-9)
Pritchard-Jones_cd-24-0878_supplementary_figures_1-9_suppsf1.pdf Access restricted to UCL open access staff until 13 December 2025. Download (16MB) |
![[thumbnail of Supplementary Tables 1-8]](https://discovery-pp.ucl.ac.uk/style/images/fileicons/other.png) |
Spreadsheet (Supplementary Tables 1-8)
Pritchard-Jones_cd-24-0878_supplementary_tables_1-8_suppst1.xlsx Access restricted to UCL open access staff until 13 December 2025. Download (8MB) |
Abstract
Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumourigenesis. To investigate this, we assembled a cohort of 137 children with Wilms tumour, of whom 71 had a pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukaemias), utilising WGS, RNA sequencing and genome wide methylation, validating our findings in an independent cohort. Tumour development differed in children harbouring a predisposition, depending on the variant gene and its developmental timing. Differences pervaded the repertoire of driver events, including high risk mutations, the clonal architecture of normal kidneys, and the relatedness of neoplasms from the same individual. Our findings indicate that predisposition may preordain Wilms tumourigenesis, suggesting a variant specific approach to managing children merits consideration.
| Type: | Article |
|---|---|
| Title: | Predisposition footprints in the somatic genome of Wilms tumours |
| Location: | United States |
| DOI: | 10.1158/2159-8290.CD-24-0878 |
| Publisher version: | https://doi.org/10.1158/2159-8290.cd-24-0878 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10203689 |
Archive Staff Only
 |
View Item |
