Results from the first 117 children to receive whole genome sequencing through the national GMS Childhood Cancer project show that in 90% of cases, genetic changes of clinical significance were found. The extensive work was carried out by more than 30 researchers and clinicians from across Sweden. The results are now published in JCO Precision Oncology.

GMS Childhood Cancer is a unique project that offers all children in Sweden affected by cancer whole genome sequencing as part of the diagnostic process.

David Gisselsson Nord

David Gisselsson Nord. Photo: Åsa Hansdotter, Lund University.

“The most surprising result from the first summation of the project was how often the tumor’s gene sequence could be used as part of the diagnosis, for either a safer or more accurate classification of the tumor. A unique feature of the study is that almost all children are offered sequencing at the onset of the disease, not at relapse or exacerbation as in similar international studies,” says David Gisselsson Nord, professor and senior physician at Lund University/Region Skåne, who coordinated the study.

During the period January 2021 to March 2022, 117 children were included in the study and their tumors were analyzed by whole genome sequencing. For about half of the children who received whole genome sequencing, clinically relevant genetic changes were found that either indicated a specific subgroup for diagnosis, were linked to prognosis or to a specific treatment target. In another 40%, the diagnosis already made was confirmed.

“In a few cases, the diagnosis and treatment changed completely. In other cases, this meant that the child could receive targeted cancer drugs. In addition, a number of cases of congenital genetic diseases were discovered that required special treatment,” says David Gisselsson Nord.

Traditional radiation and chemotherapy treatments are effective for children, but often come with lifelong side effects that can occur immediately or years after treatment. There are currently few clinical trials for children, which means that even if new treatment targets are found with whole genome sequencing, children cannot always access targeted treatments.

“However, we see more and more targeted drugs becoming available for children with cancer. Sequencing means that we can now effectively pair the right child with the right drug,” says David Gisselsson Nord.

Children from all over Sweden are included in the project via the six pediatric oncology centers. Sequencing and bioinformatics were then carried out at three centers and since the article was written, a fourth center for sequencing has also started. To be a resource for researchers, data from the study is also uploaded to the Swedish Childhood Tumor Biobank (Barntumörbanken), which has played an important role in the realisation of the study.

Bioinformatics analysis and interpretation tools are crucial to ensure that the large amount of sequencing data generated can provide the right support to treating physicians. Within the project, the SciLifeLab Clinical Genomics platform and Genomic Medicine Centers (GMCs) across Sweden have developed and harmonized bioinformatic analyses and developed better tools for clinical variant interpretation, which will support decision-making.

Valtteri Wirta

Valtteri Wirta. Photo: Niklas Norberg Wirtén, SciLifeLab.

“The work we are doing to harmonize bioinformatics and interpretation tools across the country means that we will be able to ensure that all patients have access to uniform and high-quality analyses of equal standard,” says Valtteri Wirta, co-chair of GMS Informatics and Platform Scientific Director at SciLifeLab Clinical Genomics Stockholm.

The GMS Childhood Cancer project continues and more children with cancer are continuously included. From 2022, leukemias are also included. An important part of the project going forward will be the health economic analyses that will show which patient groups will have the greatest clinical benefit from whole genome sequencing in the future.

“Through the extensive collaboration across Sweden, we will be able to accelerate the national introduction of whole genome sequencing in the care of children with cancer,” concludes Valtteri Wirta.

The work has been led by David Gisselsson Nord, professor of molecular pathology at Lund University and senior physician in pathology at Region Skåne, together with Johanna Sandgren, head of the Swedish Childhood Tumor Biobank, and Gustaf Ljungman, professor at Uppsala University and senior physician at Uppsala University Hospital.

The project is funded by the Swedish Childhood Cancer Fund (Barncancerfonden) and the Swedish Ministry of Social Affairs.

Diagnostic Yield from a Nationwide Implementation of Precision Medicine for all Children With Cancer. Elisabeth Wadensten, Sandra Wessman,Frida Abel, Teresita Diaz De Ståhl, Bianca Tesi, Christina Orsmark Pietras, Linda Arvidsson, Fulya Taylan, Susanne Fransson, Hartmut Vogt, Anna Poluha, Sailendra Pradhananga, Maria Hellberg, Kristina Lagerstedt-Robinson, Praveen Raj Somarajan, Sofie Samuelsson, Sara Orrsjö, Khurram Maqbool, Karin Henning, Tobias Strid, Torben Ek, Henrik Fagman, Thomas Olsson Bontell, Tommy Martinsson, Florian Puls, Per Kogner, Valtteri Wirta, Cornelis Jan Pronk, Joakim Wille, Richard Rosenquist, Monica Nistér, Fredrik Mertens, Magnus Sabel, Ulrika Norén-Nyström, Pernilla Grillner, Ann Nordgren, Gustaf Ljungman, Johanna Sandgren, David Gisselsson. JCO Precision Oncology, online 29 juni 2023,

Photo: iStock