Understanding Wilms Tumors: The Role of Genes and Imprinting in Childhood Kidney Cancer

Recent research conducted at the University of Würzburg, in collaboration with the Wellcome Sanger Institute in the UK, has provided new insights into the development of Wilms tumors, a form of malignant kidney cancer affecting young children. These findings are crucial for improving risk assessment, early detection, and personalized treatment. The study utilized samples from the extensive Wilms tumor biobank at the JMU Biocenter, which has been collecting tissue samples from around 1,800 affected children since 1994, including familial and bilateral cases with genetic predispositions. The researchers successfully identified hereditary factors in over 90% of cases, revealing the complex genetic and epigenetic mechanisms involved.

Wilms tumor development follows a multi-step process, consistent with Alfred Knudsen's "two-hit hypothesis." Most commonly, mutations are found in WT1, a tumor suppressor gene, where one copy is inactivated in all body cells. When the second copy in kidney cells fails and the growth-promoting factor IGF2 is activated simultaneously, precursor tumors form. Further activation of the WNT signaling pathway then drives malignant transformation.

An intriguing discovery was that about a third of cases did not show classic hereditary mutations but involved disruptions in the genomic imprinting of the IGF2 gene. Imprinting is epigenetic and established during embryonic development, meaning these disturbances are not inherited but can cause mosaics of altered and normal cells. When mutations occur in kidney cells with impaired IGF2 regulation, tumors can develop.

The findings underscore the importance of genetic screening for children at risk. As Professor Manfred Gessler emphasizes, identifying hereditary patterns early enables better monitoring and prevention of secondary tumors or early kidney failure.

This research advances our understanding of the genetic and epigenetic pathways leading to Wilms tumors, highlighting potential for targeted therapies and personalized medical approaches. It also advocates for comprehensive molecular testing of blood and tumor samples to identify at-risk children and improve clinical outcomes.

Source: https://medicalxpress.com/news/2025-05-wilms-tumors-genes-imprinting-pave.html