Readouts of the full DNA of children with cancer at diagnosis have been implemented as the standard of care in a European first. By determining a child's type of cancer as precisely as possible, the Princess Máxima Center for pediatric oncology aims to offer each individual child the treatment most likely to work for them.
To determine the precise form of childhood cancer, the DNA in children's tumor cells is analyzed at diagnosis. Since May, the Princess Máxima Center has started analyzing all children's complete tumor DNA as standard of care, using a technology called whole genome sequencing.
The Máxima Center made the switch because whole genome sequencing is more comprehensive than the traditional technique, in which only the protein-coding part of the DNA, which makes up roughly 2% of the complete DNA, was analyzed. As well as improving diagnostics, the move will also provide valuable data for the development of new treatments and for research into how childhood cancer develops.
Dr. Bastiaan Tops, head of the Laboratory for Childhood Cancer Pathology at the Princess Máxima Center for pediatric oncology: 'By analyzing the full DNA, we can now uncover all genetic changes in the tumor cell. This switch gives a more comprehensive picture of a child's cancer. This approach enables applications like pharmacogenomics, where we can offer treatments based on a child's genetic profile. It also allows us to more closely monitor tumor progression during treatment at a molecular level.'
Pharmacogenomics
Whole genome sequencing looks not only at the DNA of the tumor cells, but also at so-called germline DNA in a child's healthy cells. This enables pharmacogenomic analyses, which help to provide a precision medicine treatment according to the child's inherited genetic profile.
Dr. Meta Diekstra postdoctoral researcher in the Huitema group and hospital pharmacist at the Princess Máxima Center for pediatric oncology, leads the clinical implementation of pharmacogenetic testing, with support from the Princess Máxima Center Foundation.
A major advantage of using whole genome sequencing at diagnosis is that we can reuse the data for pharmacogenomic analyses. With specialized software, we can quickly and reliably scan the data for genetic variants that affect how a child responds to different drugs, both in terms of side effects and efficacy. This lets us tailor treatment more precisely, from adjusting the dose to choosing a different drug that better matches a child's genetic profile."
Dr. Meta Diekstra postdoctoral researcher in the Huitema group and hospital pharmacist at the Princess Máxima Center for pediatric oncology
Research data and infrastructure
Analyzing the full tumor DNA at diagnosis also offers scientists new insights into genetically inherited forms of childhood cancer and new leads for immunotherapy research.
Dr. Patrick Kemmeren, research group leader and head of the Big Data Core: 'Implementing whole genome sequencing at diagnosis would not have been possible without the close collaboration between our computational biology group and our diagnostics colleagues. Together, we developed a unique data infrastructure setup that is shared between departments and ensures that genetic information about a child's tumor is not only available for research faster but also, that we can quickly implement innovations into the clinic.'
The scientists also plan to share anonymized whole genome sequencing data with other research institutions working on childhood cancer. Kemmeren stresses the importance of this: 'Childhood cancer is rare, and in addition to researching the data ourselves, we hope that by sharing this data we will accelerate the development of new treatments and gain a better understanding of how childhood cancer develops.'
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