All cells in the human body carry two copies of each gene: one from each parent. But during cell division, errors can occur, causing some sections of DNA in chromosomes to be copied more often than normal. These so-called ‘copy number gains’ are a hallmark of cancer cells.
Previous research often focused on large-scale copy number gains, but in this study, the researchers looked specifically at more subtle variations – known as low-amplitude copy number gains. Their findings show that even these small changes can give cancer cells a growth advantage and offer potential targets for treatment.
Genetic patterns
Researchers in the Looijenga group at the Princess Máxima Center collaborated with Amsterdam UMC Cancer Center Amsterdam. They found that subtle DNA gains often occur in genes already known to play a role in cancer development and growth. But they also found these changes in genes not previously linked to cancer. By linking these genetic patterns to data on how cancer cells respond to particular drugs, they were able to predict which cancers might be sensitive to existing treatments.
‘Even subtle copy number gains give cancer cells an edge over healthy cells,’ dr. Thomas Eleveld, postdoctoral researcher in the Looijenga group, explains. ‘By combining bioinformatics with large public datasets on DNA changes and drug sensitivity, we mapped which genes become more important to cancer cells when their copy number increases. We saw that cancer cells with such DNA gains are often more sensitive to drugs that target those specific genes. That opens the door to much more effective, targeted therapies.’
Smart data integration
The study used data from thousands of tumors across different cancer types, in both adults and children. For example, the researchers found that a subtle gain in a region of chromosome 1q21 in neuroblastoma – an aggressive childhood cancer – is linked to poorer survival, but also to sensitivity to a drug that blocks the MCL1 protein.
According to prof. Leendert Looijenga, research group leader at the Máxima, this study is a clear example of how fundamental science can contribute to better care for children with cancer. ‘We now have a new way to integrate unique genetic data and translate it into clinically relevant insights. That helps us make better decisions when designing clinical trials.’ At the same time, it highlights the importance of making genetic data—generated with public funding around the world—accessible, as it is not always being shared.
Toward more targeted treatment
The next step is to study low-amplitude copy number gains in childhood cancers in more detail, says Looijenga. ‘In the future, this approach could help us develop treatments that truly match the genetic profile of a child’s tumor. That’s essential for the most effective treatment possible, with the fewest side effects.’
The study was published this week in the journal Nucleic Acids Research and was supported in part by the Dutch Cancer Society (KWF).