A common gene found in organisms as diverse as worms to humans is offering valuable clues to the origins of kidney development. It could have implications for children with kidney cancer and kidney regeneration in adults, a new study found.
The research team, led by George Q. Daley, MD, PhD, of Boston Children's Hospital analyzed a gene called Lin28, which they say is linked to nearly one-third of cases of Wilms tumor, a pediatric kidney cancer.
Lin28 is closely tied to organ and tissue development and is active in the kidneys during early development.
To see if Lin28 might be a factor in Wilms tumor development, Daley and an international team of collaborators measured the gene's expression in tumor samples from 105 Wilms patients.
Nearly one-third of the tumors examined in the study exhibited high levels of Lin28 activity, according to the study.
Each year an estimated 500 children in the United States are diagnosed with Wilms tumor, also known as nephroblastoma.
Wilms tumors tend to occur in young children, with average diagnosis at 3-4 years of age. It becomes less common as children grow older and is uncommon after age 6. Nephroblastoma is very rare in adults, although cases have been reported.
When doctors examined the tumors under a microscope, they resemble immature (embryonic) kidneys, leading them to conclude Wilms tumors form during fetal development then persist into childhood.
By the time the tumors are detected in children, they are often quite large, weighing one pound on average.
Daley and colleagues engineered mice to express Lin28 in their kidneys. They eventually developed Wilms tumor. But when Lin28 was withdrawn, the tumor decreased in size and severity, indicating that blocking or deactivating the gene holds therapeutic promise for children with Wilms.
"Our data suggest that when Lin28 is active for too long, it keeps the kidneys from completing their developmental program, which would explain Wilms tumors' resemblance to embryonic kidney tissues" said Achia Urbach, PhD, lead author on the study and former Boston Children’s researcher.