A recent study from Boston Children’s Hospital suggests that nearly 1/3 of pediatric nephroblastomas are associated with a gene called Lin28. Transgenic mice whose kidneys expressed Lin28 developed pediatric nephroblastoma, and the mice recovered when Lin28 was silenced, suggesting that blocking or inhibiting this gene may hold promise for the treatment of pediatric nephroblastoma patients. Studies in mouse models further suggest that Lin28 promotes kidney development, which may provide some clues to regeneration of injured kidneys in adults. Nephroblastoma is the most common malignant tumor of the pediatric urinary system, an embryonic malignant mixed tumor, second only to neuroblastoma in incidence, and is also known as nephroblastoma, nephroblastoma, and renal mixed tumor.Rance first described this tumor in 1814. Rance first described the tumor in 1814, and by 1899 Max Willms had described the characteristics of the tumor in more detail, so it was named Wilms tumor, Recently, according to a study at Boston Children’s Hospital, nearly one-third of pediatric nephroblastomas are associated with a gene called Lin28. Transgenic mice whose kidneys expressed Lin28 developed pediatric nephroblastoma, and the mice recovered when Lin28 was silenced, suggesting that blocking or inhibiting this gene may hold promise for the treatment of pediatric nephroblastoma patients. Studies in mouse models further suggest that Lin28 promotes kidney development, which may provide some clues to regenerating injured kidneys in adults. A team of researchers led by Dr. George Q, Daley, of Boston Children’s Hospital, published the results of the study in a recent issue of the journal Genes & Development. In the United States, about 500 children are diagnosed with nephroblastoma each year. When viewed under a microscope, the tumors resemble immature embryonic kidney cells, so doctors believe that nephroblastomas form during kidney development, which is typically completed at birth and lasts through childhood. Lin28 is closely linked to organ and tissue development in organisms as diverse as worms and humans, remaining active in the kidneys early in development. To elucidate whether Lin28 might be a factor in the development of nephroblastoma, Daley and an international team of research collaborators examined the gene’s expression in tumor samples from 105 patients with nephroblastoma. Nearly one-third of the tumors were found to exhibit high levels of Lin28 activity. Dr. Daley, who is head of the Stem Cell Transplantation Program at Boston Children’s Hospital and an investigator at the Howard Hughes Medical Institute, noted, “We found a specific association between Lin28 and high-risk ‘blastemal (embryonic)’ nephroblastoma. These tumors tend to be resistant to treatment, but currently cannot be identified prior to treatment.Lin28 may serve as a biomarker for such treatment-resistant tumors.” Achia Urbach, Ph.D., lead author of this study, designed a mouse model with the Lin28 gene expressed in the kidneys. The kidneys of these mice were significantly enlarged and continued to enlarge as long as Lin28 was active. Eventually, these kidneys exhibited the appearance of a nephroblastoma. According to Urbach, a former researcher at Boston Children’s Hospital and at Israel-Boylan University, “Our data suggest that when Lin28 is active for too long, it inhibits the kidneys from completing their developmental program, which could explain why nephroblastomas share similarities with embryonic kidney tissue.” Lin28 is part of a feedback loop that features a tumor suppressor gene called Let-7, and each of these two genes constrains the other.Daley and Urbach’s group found that by forcing Let-7 expression in their transgenic mouse model, they were able to reverse the tumorigenic effects of Lin28, suggesting that targeting Lin28 holds promise for the treatment of nephroblastoma. The team’s insights into the origin of renal cell carcinoma have important implications for promoting kidney growth and regeneration. Functional units of the kidney, called renal units, are formed only during development and cannot be regenerated in the adult body if injured by kidney disease. The need for dialysis or kidney transplants as a result of kidney failure is a major burden on the health care system. Daley’s group found that a brief control pulse of Lin28 expression in their mouse model increased the number of kidney units in newborn mice. Further experiments manipulating Lin28 could provide more insight into renal unit formation, potentially restoring the normal number of renal units or, alternatively, regenerating injured adult kidneys. Adult kidney injury can cause scarring rather than healing, and if there is a lot of scarring, it can lead to kidney failure,” Daley noted. Further Lin28 studies will tell us important information about kidney development, pointing to new potential interventions for kidney disease.”