Scientists at the Wellcome Sanger Institute have made meaningful discoveries about Wilms’ tumor, a form of kidney cancer that mainly affects children under the age of five. The study compared the genome sequences of normal kidney tissue to tumor tissue and located a patch of tissue carrying the DNA sequences causing Wilms’ tumor. The researchers recently published their findings in Science.
Childhood kidney cancers are rare, but Wilms’ tumor is the most common, affecting about 500-600 children per year in the United States. Most cases are curable via surgery, chemotherapy and radiation. It was previously assumed that the cause of Wilms’ tumor was an early cell mutation as the kidneys are developing. This study has shown that the cancer forms in the first weeks of life when an early cell gains a DNA modification associated with Wilms’ tumor, and then that cell proliferates.
This study is the first of its kind to compare healthy kidneys with Wilms’ tumor tissue, using 66 tumor and 163 normal kidney tissue samples. In two thirds of the children with Wilms’ tumor, the DNA changes associated with the disease were found in the normal and tumor tissue. The researchers then focused on these genetically abnormal cells, which appeared normal under a microscope.
A Single DNA Change
While these cells appeared to be normal, they were found to have developed a single rouge cell with a mutation suppressing the H19 gene. Normally, H19 works to make sure the cells grow in an orderly manner. With H19 suppressed, the cells start growing quickly, causing pre-cancerous tissue to form and leading to Wilms’ tumor.
This understanding of the precise start of Wilms’ tumor provides a marker for kidney tissue that is higher risk. This causes a shift in the understanding of Wilms’ tumor and childhood cancers overall as scientists continue to develop therapeutics and treatment options. According to lead author, Dr. Sam Behjati, “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.”
Since Wilms’ tumor has a relatively high probability or recurrence, it is normally treated by removing the whole kidney. For most people, this is okay and they can proceed with a relatively normal life. However, for the 10% of people with Wilms’ tumor that affects both kidneys, removal is life-altering.
The results of this study open the door for the discovery of better treatment options with the hope that one day treatment could focus on this small patch of tissue instead of kidney removal.
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