A nationwide study from Karolinska Institutet shows that genetic testing can identify germline predisposition underlying childhood leukemia. The findings, published in Nature Communications, could help enable more personalized treatment and long-term follow-up.
Researchers studied 181 children in Sweden who had recently been diagnosed with acute leukemia. The study combined three approaches: clinical assessment of symptoms and family history, whole-genome sequencing (analysis of the entire genome), and genetic analysis of tumor tissue. Overall, the researchers found that 9 of the 181 children (approximately 5 percent) carried genetic variants indicating a germline predisposition to leukemia. Six of these children had genetic aberrations specifically associated with leukemia, while three carried rare variants in genes previously linked to solid tumors.
"We found that germline predisposition to childhood leukemia is relatively uncommon, but when present they can have major implications for the individual child," says Ann Nordgren , Professor at the Department of Molecular Medicine and Surgery, Rare Diseases Research Group, Karolinska Institutet, who led the study.
In six of the nine children, the increased cancer risk had not been recognized before the leukemia diagnosis. Once identified, the findings led to changes in clinical management: eight children were enrolled in specialized surveillance programs, and four received modifications to their treatment.
"Our results show that genetic testing can provide clinically important information that influences both treatment and follow-up. At the same time, the benefits need to be weighed against available resources and the need for genetic counselling," says Bianca Tesi , consultant clinical geneticist at the Department of Clinical Genetics and Genomics, Karolinska University Hospital, and co-senior author of the study.
Previous studies have estimated that between four and ten percent of children with hematological malignancies have a germline cancer predisposition, although reported frequencies vary depending on study design and patient selection. In the present study, the proportion was somewhat lower, which the researchers believe is partly because all children were included regardless of whether there was any prior suspicion of hereditary cancer risk.
"By sequencing every child and combining comprehensive clinical evaluation with whole-genome sequencing and tumor analysis, we obtained a complete picture of how common germline variants are and which genes are involved," says Fulya Taylan , Associate Professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and the first author of the study.
One limitation of the study is that the analyses focused on a predefined list of genes, meaning that some genetic causes may have been missed. The researchers also emphasize that larger studies are needed to better understand the contribution of germline genetic factors to childhood leukemia.
The study was carried out in collaboration between six Swedish university hospitals and research groups within Genomic Medicine Sweden. It was funded by the Swedish Childhood Cancer Fund, public research funding, and other grant agencies. The authors report no major competing interests.
Publication
Diagnostic yield of cancer predisposition in a nationwide prospective childhood acute leukemia cohort Taylan, F., Staffas, A., Sjögren, S. et al. Nat Commun 17, 10280 (2026). doi.org/10.1038/s41467-026-78170-z
