Genetic code of rare kidney cancer cracked

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. In the new paper, published today (25th September) in Nature Communications, 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. 

There are around 100 cases of reninoma reported to date worldwide (1), and it is amongst the rarest of tumours in humans. Although it can usually be cured with surgery, it can cause severe hypertension or it can spread and develop into metastases. There are no existing medical treatments for reninoma and management involves surgery alone. Until now, it had been unknown what genetic error causes reninoma. 

In the new study, a collaboration between the Wellcome Sanger Institute and Great Ormond Street Hospital and The Royal Free Hospital, funded by The Little Princess Trust, researchers found that there is a specific error in the genetic code of a known cancer gene, NOTCH1,  that is behind the development of this rare cancer. 

The team examined two cancer samples — from a young adult and a child (2) — with advanced genomic techniques, known as whole genome and single nuclear sequencing (3). Their findings suggest that the use of existing drugs targeting this specific gene is a possible solution to treating reninoma for patients where surgery is not a viable option. 

Taryn Treger, first author of the study and The Little Princess Trust Fellow at the Wellcome Sanger Institute, said: “Many cancerous tumours have already been deciphered with genomic technologies, however, this is not so true in rare cancers, particularly those affecting children. Our work aims to fill that gap. This is the first time that we have identified the drivers for reninoma and we hope that our work continues to pave the way towards new therapies for childhood cancers.”

Dr Tanzina Chowdhury, co-lead author of the study, at Great Ormond Street Hospital, said: “Rare kidney cancers known as reninomas do not respond to conventional anti-cancer therapies. The only known treatment at the moment is surgery. Our study shows that, actually, there is a specific and well-studied gene that drives this rare cancer. If we use already known drugs that affect this gene, we might be able to treat it without the need for an invasive technique such as surgery.”

Dr Sam Behjati, co-lead author of the study, Wellcome Senior Research Fellow at the Wellcome Sanger Institute and Honorary Consultant Paediatric Oncologist at Addenbrooke’s Hospital, said: “Rare cancers are exceedingly challenging to study, and patients with such tumours may therefore not benefit from cancer research. Here, we have a powerful example of cutting-edge science rewriting our understanding of an ultra rare tumour type, reninoma, whilst delivering a finding that potentially has immediate clinical benefits for patients.”

Phil Brace, Chief Executive of The Little Princess Trust, said: “We are committed to funding research searching for more effective treatments for all childhood cancers and so we are delighted to hear of the discoveries that have been made. We also want to help researchers find kinder solutions for young people and so we are very pleased to hear there may be ways to treat this rare kidney cancer without the need for surgery.”  

ENDS

Contact details:
Jelena Pupavac
Press Office
Wellcome Sanger Institute
Cambridge, CB10 1SA
Email: press.office@sanger.ac.uk

Notes to Editors:

1. Inam, R., Gandhi, J., Joshi, G., Smith, N. L. & Khan, S. A. Juxtaglomerular Cell Tumor: Reviewing a Cryptic Cause of Surgically Correctable Hypertension. Curr. Urol. 13, 7–12 (2019).

2. The samples came from a young child with a localised tumour from the UMBRELLA study and a young female adult with metastatic (lung) reninoma. 

3. Whole genome sequencing is a method that analyses the entire genome of an organism. Single nucleus sequencing is a method that uses isolated nuclei - the part of the cell that contains our DNA information - instead of whole cells to understand genes and their functions.  

Publication: Treger, T.D., et al (2023). ‘Targetable NOTCH1 rearrangements in reninoma.’ Nature Communications. DOI: 10.1038/s41467-023-41118-8

Funding:

This project was funded by The Little Princess Trust (grant number CCLGA 2019 27) and the Wellcome Trust Grants (grants 206194; 108413/A/15/D; 223135/Z/21/Z). 

Selected websites:

About Great Ormond Street Hospital (GOSH)
Great Ormond Street Hospital is one of the world’s leading children’s hospitals with the broadest range of dedicated, children’s healthcare specialists under one roof in the UK. The hospital’s pioneering research and treatment gives hope to children from across the UK with the rarest, most complex and often life-threatening conditions. Our patients and families are central to everything we do – from the moment they come through the door and for as long as they need us.  

About the UCL Great Ormond Street Institute of Child Health (UCL GOS ICH)
The UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) is part of the Faculty of Population Health Sciences within the School of Life and Medical Sciences at University College London. Together with its clinical partner Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), it forms the UK's only paediatric National Institute for Health Research Biomedical Research Centre and has the largest concentration of children's health research in Europe. For more information visit www.ucl.ac.uk/child-health

About The 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. The Little Princess Trust’s funding is driven by improving patient outcomes, identifying unmet needs, and answering unanswered questions. 

The Wellcome Sanger Institute
The Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast – we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at www.sanger.ac.uk or follow us on Twitter, Facebook, LinkedIn and on our Blog.

About Wellcome
Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health. https://wellcome.org/