Kidney cells showing Wilms Tumour on a histology microscope slide. Image credit: Nephron, CC BY-SA 3.0, via Wikimedia Commons

Wilms Tumour. Image credit: Nephron, CC-BY_3.0, via Wikimedia Commons
Categories: Sanger Science25 September 2023

One childhood cancer, one thousand children: landmark genomic study delivers first discoveries

Tumours from 1000 children with kidney cancer have been sequenced, thanks to the Little Princess Trust and researchers at the Wellcome Sanger Institute. The Little Princess Trust ‘Knowledge Bank’ is the largest comprehensive genomics resource for any childhood solid tumour, and is already being used for research to understand childhood cancers.

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Wilms Tumour is the most common kidney cancer in children - each year in the UK, around 100 children will be diagnosed. Standard treatment involves surgery, along with chemotherapy and/or radiotherapy. With this treatment approach,  almost 90 per cent of children will be expected to survive. But despite this encouraging number, many children will not survive their disease, and it does not account for the psychological impact of treatment on children and their parents, as well as the significant long term health issues often encountered after the cancer is cured.

The initial events underlying Wilms Tumour are thought to arise in the embryo, when the normal pathway of kidney development is interrupted. Its causes are genetic, rather than environmental, and whilst a large number of causative DNA alterations have been identified, each one only explains a subset of cases. We remain very much in the dark about the full spectrum of genomic alterations that cause the emergence, growth and spread of this childhood tumour.

In 2019, an international team led by Sanger Institute Group Leader, Dr Sam Behjati set out to fill this knowledge gap. Funded by a grant from The Little Princess Trust, a charity which provides wigs for children who have lost their hair and funds research into better treatments for all paediatric cancers, the team wants to understand the entire genetic landscape of Wilms Tumour.


December 2019: Root of childhood kidney cancer discovered

Sanger Institute scientists, working with researchers at Addenbrooke's Hospital in Cambridge and Great Ormond Street Hospital in London have discovered pre-cancerous signatures in healthy tissue that point the way towards new treatment options

The aim of the ongoing project is to create The Little Princess Trust ‘Knowledge Bank’ of Wilms Tumour. Almost 3,000 samples have been received from Germany, the Netherlands and from 20 different hospitals in the UK, coordinated by Great Ormond Street Hospital. Samples were taken from the tumour (often including many different parts of the same tumour) as well as non-cancerous tissue and blood, in order to define whether a genetic mutation was inherited or not. The genomic analysis involved whole genome/exome sequencing (to understand which mutations drive the tumour’s growth), RNA sequencing (to understand which genes were active in the tumour) and, for the so-called discovery cohort, DNA methylation analysis (to explore how cancer gene activity is regulated). Together with detailed patient records, this extensive approach is contributing to a unique holistic classification of Wilms Tumour biology. Excitingly, the team has just logged its thousandth sequenced individual, which represents a landmark in childhood cancer studies.

“We have achieved a critical milestone with the completion of data generation for The Little Princess Trust Knowledge Bank of Wilms Tumour. Studying 1,000 children with a rare cancer is an extraordinary and unparalleled success.”

Dr Sam Behjati,
Group Leader, Wellcome Sanger Institute

With a thousand individuals now sequenced, and analyses ongoing, the team is already providing exciting insights into Wilms Tumour as well as into other renal tumours. For example, in a recent paper led by Dr Taryn Treger, who works in the Behjati lab as The Little Princess Trust Fellow  the team discovered the specific genetic cause behind reninoma, an ultra-rare kidney tumour for which surgery is currently the only available option. Pinpointing the genetic cause has opened up the potential for appliyng existing drugs to treat it, a powerful example of the therapeutic potential of their genome-based studies.


September 2023: Genetic code of rare kidney cancer cracked

The genetic code of a rare form of kidney cancer, called reninoma, has been studied for the first time. Researchers at the Wellcome Sanger Institute, Great Ormond Street Hospital and The Royal Free Hospital also revealed a new drug target that could serve as an alternative treatment if surgery is not recommended

“Through our research, we hope to treat children more accurately - giving less treatment to children with genetically less aggressive tumours, whilst intensifying treatment in more aggressive disease.”

Dr Taryn Treger,
Researcher, Wellcome Sanger Institute

The Little Princess Trust Knowledge Bank of Wilms Tumour is already the largest comprehensive genomics resource for any childhood solid tumour worldwide, and is still growing. The team hopes this ‘Knowledge Bank’ will not only revolutionise our understanding and treatment of Wilms Tumour but will set a precedent for how we treat all childhood cancers.

“We are indebted to the children and families who donated their tissue to research and to The Little Princess Trust and their incredible supporters for funding our endeavour.”

Dr Sam Behjati,
Group Leader, Wellcome Sanger Institute


Little Princess Trust

The Little Princess Trust gives Hair and Hope to children and young people by providing wigs and funding vital research into childhood cancers.
Since 2016, the charity has given more than £20million to research focused on finding kinder and more effective treatments for all childhood cancers.

“We are very proud to fund this work and are delighted to hear that the team has reached the milestone of logging its 1,000th sequenced individual. This tremendous research is increasing our knowledge of Wilms Tumour and we hope it will lead to kinder and more effective treatments for all those young people whose lives are so cruelly affected by cancer.”

Phil Brace,
Chief Executive, The Little Princess Trust

The Sanger Institute researchers are now looking forward to using the Knowledge Bank to make fundamental discoveries into Wilms Tumour biology.

“Now that the data have been generated, the number crunching can begin. We want to crack the genetic code of Wilms tumour to provide better and more personalised treatments to children with this kidney cancer.”

Dr Sam Behjati,
Group Leader, Wellcome Sanger Institute

Taryn is also looking to the wider impacts of the work.

“In the longer term, we envision that the Little Princess Trust Knowledge Bank of Wilms Tumour will serve as a blueprint for advancing our understanding of various different childhood cancers.”

Dr Taryn Treger,
Researcher, Wellcome Sanger Institute

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