Breakthroughs in Wilms tumor research: children of parents affected!

Breakthroughs in Wilms tumor research: children of parents affected!

A research team from the University of Würzburg has made significant progress in the study of kidney tumors, particularly Wilms tumor. This form of kidney cancer primarily affects children under the age of five and is one of the most common types of cancer at this age. Around 100 children in Germany develop this tumor every year. How uni-wuerzburg.de reports, the scientists are analyzing the hereditary predisposition to Wilms tumors using samples from the Wilms Tumor Biobank collected over three decades, from 1994 to 2022.

In total, samples from around 1,800 affected children were examined. The researchers were able to identify 20 familial tumors and 109 bilateral tumors. It is noteworthy that over 90% of the cases had genetic predispositions. These results support the “two-hit hypothesis” formulated by Alfred Knudsen to explain tumorigenesis. A common mutation in a tumor suppressor gene, the WT1 gene, has been identified. The inactivation of both WT1 copies, together with the activation of the growth factor IGF2, represents a key factor for tumor formation.

Genetic findings and their implications

The research also showed that genetic changes in the germline were detected in about 50% of patients. However, a third of the children had disorders of the genomic imprinting of the IGF2 gene, which are not hereditary. These epigenetic predispositions often lead to “mosaics” of normal and disturbed IGF2 expression, which can mutate in kidney cells and develop tumors. Children with this particular neuropathological constellation have an increased risk of second tumors and early kidney failure, which is further intensified by the genetic abnormalities in both generations of siblings. The researchers therefore recommend molecular examinations of blood and tumor samples to identify high-risk cases at an early stage.

Another important aspect of the study is the role of genetic changes in the treatment and prognosis of the disease. Tumors with WT1 gene changes form a separate subgroup, while other tumors are characterized by diverse, partly unknown mutations. Gene expression patterns and DNA methylation are crucial to differentiate into genetically defined subgroups, supporting the development of tailored treatment plans. Such strategies aim to minimize side effects while ensuring effective treatments.

Collaborations on this research include the Wellcome Sanger Institute and other institutions including Cambridge University Hospitals NHS Foundation Trust and Great Ormond Street Hospital. These interdisciplinary efforts aim to develop improved risk assessment and targeted screening for affected children.

A look into the future

The results of the study indicate that genetic analyzes and a better understanding of the biology of Wilms tumors are of great importance not only for those affected, but also for their siblings and offspring. In the long term, these findings could help to establish effective screening programs that make it possible to detect genetic predispositions at an early stage. This could not only improve treatment outcomes, but also reduce the risk of secondary cancers.

The original publication of the research appeared in “Genome Medicine” and reflects a fundamental change in the way we view genetic diseases such as Wilms tumor. Ultimately, such studies create the basis for selecting more precise and patient-centered therapeutic approaches in the future. Support from organizations such as the Little Princess Trust, Wellcome, the DFG and the BMBF plays a crucial role in promoting this important research work.