Researchers map genetic differences between children with Wilms tumor

Researchers map genetic differences between children with Wilms tumor

Genetically tailored treatment plans for children with a type of kidney cancer could help provide the most effective care while minimizing side effects as much as possible.

Researchers from the Wellcome Sanger Institute, the NHS Foundation Trust, Great Ormond Street Hospital, the University of Würzburg, and their collaborators have mapped the genetic differences between children with a type of childhood kidney cancer called Wilms tumor.

In about 30 percent of children with Wilms tumor, there is an inherited genetic change that increases the risk of developing this cancer. This study, published today (January 23) incancer detection,A journal from the American Association for Cancer Research suggests that inherited genetic changes predetermine how these tumors develop, how responsive they are to certain treatments, and whether the affected person has a higher risk of secondary cancers later in life.

The team points out that different genetic predispositions lead to different tumor development pathways and kidney structures and have identified those that limit the growth of tumors. They also found that Wilms tumors develop differently in those without genetic predispositions.

Their findings suggest that tailoring treatment and screening programs to a child's genetic makeup could ensure everyone receives the most effective care. In the future, this research could help develop new therapies for certain genetic changes and identify children who may need less invasive surgery.

Wilm's tumor is a type of kidney cancer that largely affects children under the age of five. In the UK, around 85 children are diagnosed with Wilms tumor each year.

While these tumors can occur due to a spontaneous genetic change during development in the womb, in about 30 percent of cases, an underlying genetic predisposition may increase the risk of developing WILMS tumor. Traditionally, children with Wilms tumor are screened for predisposition if they have specific features such as tumors in both kidneys.

Currently, treatment of Wilms' tumor in predisposed children must balance removing enough kidney tumor to reduce the risk of secondary tumors later in life while preserving as much kidney function as possible. Strategies to spare normal kidney tissue include chemotherapy, certain types of surgery and extended courses of postoperative chemotherapy, as well as close monitoring for recurrence.

The clinical management of children with a known predisposition differs from that of children with a spontaneous genetic change due to the increased risk. By understanding more about how genetics influence Wilms tumor development, researchers could identify those at lower risk of secondary tumors and use this to inform surgical approaches and screening programs, leading to the development of new therapies.

In this new study, researchers genetically mapped several hundred tissue samples from 137 children with Wilms tumor. This included 71 children with a genetic predisposition, some of whom had early symptoms.

The team showed that tumor development differed in children with a genetic predisposition. This depended on which gene was affected and when that gene was activated during development in the womb, known as the developmental time point.

Different genetic predispositions to Wilms' tumor were found to result in specific childhood DNA changes that caused tumor formation. These DNA changes are called driver mutations, some of which increased the children's risk of secondary cancers such as Wilms tumor. In particular, genetic changes in genes –Wt1AndTrim28– led to the accumulation of additional driver mutations in specific pathways that could target future drug development.

Genetic predisposition also affected the tissue architecture of the kidneys, which could explain why some children develop non-cancerous kidney growths before cancerous tumors.

Overall, their results show that predisposition can determine how Wilms tumor develops, with specific patterns depending on the genetic variation. The researchers suggest that in the future it may be possible to tailor treatment and screening programs to the type of genetic predisposition a child has to ensure they receive the most effective care.

Dr. Taryn Treger, co-first author at the Wellcome Sanger Institute, said: “Certain genetic changes that children are born with Genetic change is.

Phil Brace, chief executive of the Little Princess Trust, which supported this research, said: "Childhood cancer treatment can have significant adverse effects, affecting the child living with the condition and people around them. We believe it is crucial to fund studies that are not only looking for ways to improve a young person's chance of survival, but also to reduce the side effects of treatment.

Our research demonstrates the power of collaborative genomic research to answer important clinical questions. At the moment we treat all children equally, which means that some children are overtreated and others are undertreated. Our results show that we may be able to personalize treatment based on genetic information. Now that we know the exact sequence of genetic changes that lead from predisposition to cancer, we may be able to more effectively target tumors and even entertain the possibility of prevention. “

Professor Sam Behjati, co-senior author at the Wellcome Sanger Institute and Cambridge University Hospitals NHS Foundation Trust

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