Hereditary predisposition seen in one-third of pediatric patients with a Wilms’ tumor
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Among 126 children diagnosed with a Wilms’ tumor, 42 showed hereditary factors, according to data published in the Journal of Clinical Oncology.
Further, researchers of the study noted all pediatric patients with a Wilms’ tumor in the Netherlands now have access to extensive genetic diagnostics.
“Wilms’ tumor (nephroblastoma) arises from a developmental arrest in the embryonic kidney1 and is frequently associated with (epi)genetic predisposing factors. Our understanding of Wilms’ tumor predisposition continues to evolve, as illustrated by the identification of novel Wilms’ tumor predisposition genes (TRIM28, REST and CTR9), the role of mosaic aberrations, and the range of phenotypic variability,” Janna A. Hol, MD, PhD candidate in the Van den Heuvel-Eibrink and Kuiper groups at the Princess Máxima Center, and colleagues wrote. “We performed a phenotypic and genomic characterization of a 5-year nationwide Wilms’ tumor cohort by a stepwise approach including targeted diagnostic testing and, after informed consent, whole-exome sequencing (WES) of germline and parental DNA (trio-analysis).”
In the observational whole-exome sequencing in children with kidney tumors study (WES-KIDTS), researchers evaluated 128 pediatric patients diagnosed with a Wilms’ tumor (71 were girls) between 2015 and 2020 in the Netherlands.
A clinical geneticist examined all patients and provided researchers with phenotypic data, disease characteristics and diagnostic test results for each patient. In situations where targeted diagnostic testing did not identify genetic predisposition, researchers used germline (trio-)whole-exome sequencing and Beckwith-Wiedemann spectrum testing on normal kidney-derived DNA. Using a WES-based 30-gene Wilms’ tumor gene panel, researchers assessed patients’ germline DNA.
Hereditary factors found
Among the 128 patients identified with a Wilms’ tumor, one died before the study ended and another did not provide consent to be analyzed. Therefore, 126 patients remained in the final analysis.
“We found hereditary factors in 42 of 126 children, so one-third of the patients,” Hol said in a press release. “That was more than we expected.”
Researchers identified DIS3L2 gene variants as a recurrent predisposing factor in five patients with a second somatic hit in four out of five tumors. The Beckwith-Wiedemann spectrum testing diagnosed 20 patients, whereas four patients without Beckwith-Wiedemann spectrum testing features showed chromosomes 11p15 methylation defects in normal kidney tissue.
Reassuring Results
According to the press release, Hol said, “For many children with a hereditary predisposition, we can reassure the family. We see, for example, that the predisposition in the child arose shortly after fertilization. Sometimes the predisposition is only found in kidney tissue, and not in blood. Then we know that siblings do not have an increased risk of developing a Wilms’ tumor. If the hereditary predisposition does come from one or both parents, siblings can get a genetic test. They are then screened extra carefully.”
“On the basis of the results of this study, we encourage standard genetic testing after counseling by a clinical geneticist for all children with Wilms’ tumor,” Hol and colleagues wrote. “In settings where this is not feasible, decision-support algorithms, such as the MIPOGG tool12, can be used to prioritize children for genetic testing.”
Reference:
- One-third of children with a kidney tumor has hereditary predisposition. https://www.eurekalert.org/news-releases/945020. Published March 1, 2022. Accessed March. 2, 2022.
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