, has uncovered a
hitherto unidentified mechanism of cancer pathogenesis in the kidney that takes
place within the first few weeks after birth. In this process, an early renal
cell acquires a carcinogenic DNA mutation that leads to its proliferation
during the development of the kidney.
For this reason,
Wilms' tumor has often been referred to as a tumor that results from one cell
'going wrong' during early kidney development.
- Elucidation of this root cause will help to develop
specific treatments as well as prevent the recurrence of Wilms' tumor
- This discovery could also pave the way for
developing screening tests for detecting cancer before it manifests
Wilms' Tumor: Key Facts
Wilms' tumor is
named after Dr. Max Wilms, the German surgeon who first described the cancer. It is also known as nephroblastoma, a
kidney cancer that mainly affects children under 5
years of age.
- Wilms' tumor is the most common type of kidney
cancer in children
- Around 80 cases of Wilms' tumor are diagnosed every
year in the UK
- 9 out of 10 cases can be cured by surgical
resection of the affected kidney along with chemotherapy and radiotherapy
- Wilms' tumor generally affects one kidney
- In about 10 percent of cases, both kidneys are affected
Salient Features of the Study
This is the first
study that compares healthy normal kidney tissue with Wilms' tumor tissue. The study was conducted by the Wellcome Sanger Institute in Hinxton,
Addenbrooke's Hospital in Cambridge, and the UCL Great Ormond Street Institute
of Child Health in London.
- Comparative genomic analysis was used to elucidate
the root cause of Wilms' tumor
- 66 tumor and 163 normal kidney tissue samples were
used in the study
- DNA from the tissue samples was sequenced, which
generated 229 whole-genome sequences
- Analysis of the genomic sequences identified
genetic differences between normal and tumor tissues arising from DNA
mutations
- The DNA mutations were shared both by normal and
tumor tissues in two-thirds of children with Wilms' tumor
- The DNA mutations were epigenetic in nature as they
arose due to non-genetic influences on gene expression
- The epigenetic DNA mutations initially occurred in
a single renal cell that suppressed the H19 gene, which prevents abnormal cell proliferation
- Suppression of the H19 gene led to abnormal proliferation of cells, resulting in
pre-cancerous patches of kidney tissue that developed into Wilms' tumor
Tim Coorens, the
first author of the paper and a PhD student from the Wellcome Sanger Institute,
said:
"A good analogy for what we found
is that Wilms' tumor is not just an isolated weed on an otherwise
well-maintained field. We discovered that the weed has an extensive root
underneath the soil. Now we know we need to look for the patch of soil where the
root has taken hold. If we remove that patch, the weed isn't going to return."
Drawbacks of Surgery and Prospects of the
New Discovery for Treating Wilms' Tumor
Wilms' tumor is
generally treated by
surgical removal of the whole affected kidney in
order to reduce the chances of recurrence. Patients with one
kidney are usually able to lead a normal life. However, in the
case
of 10 percent of patients, both kidneys need to be removed, which can have
life-threatening consequences.
Dr. Kathy
Pritchard-Jones, Professor of Pediatric Oncology at the UCL Great Ormond Street
Institute of Child Health, said:
"Surgery
for Wilms' tumor usually involves removing the whole kidney to ensure no tumor
is left behind. However, some children need more precise surgery that preserves
their kidney function, especially when they have tumors in both kidneys or are
at increased genetic risk of further tumors. This study helps us understand how
Wilms' tumors start off and provide a marker for kidney tissue that is at high
risk of forming new tumors. My hope is that in future, we'll be able to develop
treatments that focus on these patches of abnormal tissue without having to
sacrifice one or both kidneys." Concluding Remarks
Dr. Sam Behjati, lead author of the paper and Group Leader
and Wellcome Trust Intermediate Clinical Fellow from the Wellcome Sanger
Institute, said:
"The discovery of the
genetic root of Wilms' tumor signals a shift in our understanding of this
particular cancer and childhood cancer more generally. Our findings
represent a radical departure from how we think about Wilms' tumor because we
never expected to find the root of cancer in normal-looking tissue. It may even
pave the way for us to begin to think about preventing childhood cancer."
Phil Brace, Chief Executive of the Little Princess Trust,
said:
"The Little Princess Trust is very
pleased to have supported this important work. We are very excited to hear the
potential impact of what has been discovered and the improved understanding as
a result of this project. As a funder of pediatric cancer research, this was
one of our earliest supported projects and we are very keen to support more
work in this area."
Funding Source
The study was
funded by the Little Princess Trust, St. Baldrick's Foundation, Wellcome Trust,
Cancer Research UK, National Institute for Health Research, Royal College of
Surgeons of England, and Great Ormond Street Hospital Children's Charity, UK.
Reference : - Embryonal Precursors of Wilms' Tumor - (https://science.sciencemag.org/content/366/6470/1247)
Source: Medindia
