Wilms’ tumour causes a significant number of childhood deaths every year in the UK yet we still know little about why it develops. The team is investigating the very basic biology of these tumours with the aim of identifying new ‘biomarkers’ to predict disease outcome and help doctors to tailor treatments to individual children. This could also help in the development of new treatments.
The genetics of familial leukaemia
Professor Kathy Pritchard-Jones
UCL Institute of Child Health
London, WC1N 1EH
1 December 2011
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Whilst most children with Wilms’ tumour, a cancer of the kidney, can be successfully treated, this cancer is still responsible for a significant number of childhood deaths every year in the UK.
This is an excellent multi-disciplinary team that has made major contributions to our understanding of Wilms’ tumour genetics and biology.We don’t know very much about why Wilms’ tumour develops. It is believed to originate from nephrogenic rests, clusters of immature cells in the kidney in which normal development has become disrupted.
Earlier research has identified a number of damaged genes that are thought to play a role in this disrupted development, but these known genes are damaged in only a minority of Wilms’ tumours; in most cases the key genetic abnormalities have not yet been discovered.
The research team will use new technology to find out more about the genetic abnormalities that underlie the development of Wilms’ tumour.
Wilms’ tumour is the most common type of childhood kidney cancer, affecting around 80 children a year in the UK.
Wilms’ tumour – also known as nephroblastoma – is an embryonal tumour. It occurs when some of the immature cells from which the kidneys develop don’t mature and remain present in a child’s kidney after birth. These are known as nephrogenic rests. Sometimes these immature cells start to grow out of control, forming a jumbled mass of small immature cells.
As with other embryonal tumours, Wilms’ tumour predominantly affects children under the age of five years; the peak incidence is between the ages of one and three years. It usually affects only one kidney but does sometimes affect both.
Most children with Wilms’ tumour can be successfully treated with a combination of surgery and chemotherapy but around 10 children lose their lives to this type of cancer every year in the UK. There is an urgent need for new therapies to save these children.
Understanding the development of Wilms’ tumour
This is a very important and timely project that has the potential to add a great deal to our understanding of the mechanisms underlying Wilms’ tumour.
In the long run this should help towards the development of new treatments and to better targeting of current treatments to the individual.Kathy Pritchard-Jones is a Professor of Paediatric Oncology at the Institute of Child Health (ICH) where she leads a research group of international standing; she is also a Consultant Paediatric Oncologist at Great Ormond Street Hospital.
Professor Pritchard-Jones will build on earlier research that has identified a number of damaged genes that are thought to play a role in the development of Wilms’ tumours.
The genes so far identified are damaged in only a minority of cases; Professor Pritchard-Jones is working with specialist colleagues from within ICH and across UCL on this ambitious project to identify other genetic abnormalities associated with Wilms’ tumour.
The team will take advantage of a technique called next generation sequencing (NGS) which allows rapid analysis of DNA, the genetic instructions which control the development and function of our cells.
They will use NGS to identify abnormalities in the DNA of tumour cells and will then look to see whether these abnormalities are present in each patient’s nephrogenic rests.
This will enable them to determine which changes occurred at an early stage in the nephrogenic rests and which happened later in the tumour, giving vital clues about the causative events in the earliest stages of tumour development.
This work will take forward our understanding of the very basic biology of Wilms’ tumours. As a result, the research team expects to identify new ‘biomarkers’ that could be used to predict disease outcome and will help clinicians to tailor treatments to meet the needs of individual children. This could also aid the development of new treatments.
Dr Jude Fitzgibbon, Dr Matthew Smith, Dr David Taussig, Dr Jamie Cavenagh & Dr Claude Chelala, Dr Elia Stupka, Queen Mary University London/ Barts Cancer Institute; Dr Alison Male, Great Ormond Street Hospital for Children; Dr Carolyn Owen, University of Calgary.
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