The treatments that save a child's life may leave behind a biological record that lasts for decades. Scientists have discovered that platinum-based chemotherapy drugs commonly used to treat childhood cancers can cause extensive DNA damage in healthy cells, creating mutation levels normally seen only in adults and revealing a previously unknown pattern of genetic damage in the liver. "Our findings provide a potential biological explanation linking childhood cancer treatment to certain long-term health complications observed among survivors," lead study author Anna Wenger told Newsweek.
"However, our study was not designed to determine whether these mutations directly contribute to such outcomes in individual children, and further research is needed to understand their clinical significance," Wenger said. The study, published in Science, examined healthy tissues from children who had received platinum-based chemotherapy drugs such as cisplatin and carboplatin. Researchers at the University of Gothenburg found that the treatment increased mutation burdens across multiple organs and blood cells, effectively "aging" pediatric tissues at the genetic level.
Using an ultra-sensitive DNA sequencing technique known as NanoSeq, the team analyzed more than 200 platinum-exposed samples and 61 samples from children who had not received the treatment. They examined liver tissue, blood and several other organs, searching for traces of chemotherapy-induced mutations that conventional sequencing methods often miss. While platinum chemotherapy left mutational marks throughout the body, researchers identified a previously unknown DNA damage pattern, which they named "SBSA," that appeared specifically in liver tissue.
The signature was absent from blood and other healthy organs despite the drugs circulating throughout the entire body. The team found that platinum exposure increased mutation burdens in healthy tissues several-fold, with normal liver tissue showing roughly a 12-fold increase compared with untreated samples. The average platinum-exposed liver sample contained about 2,200 DNA substitutions, levels comparable to those found in adult liver tissue.
Researchers also found evidence that even limited exposure could have measurable effects. In one infant, a single cycle of carboplatin was associated with a four-fold increase in DNA mutations compared with platinum-naïve children of a similar age. Perhaps most concerning, the researchers identified thousands of mutations in genes associated with cancer.
In platinum-exposed liver tissue alone, they detected about 22,000 nonsynonymous mutations, changes that alter protein-coding DNA, including approximately 1,500 variants that would be considered pathogenic in the context of cancer. The researchers caution, however, that the presence of such mutations does not mean cancer will develop. Wenger, who is a researcher at the Sahlgrenska Center for Cancer Research at the University of Gothenburg and affiliated with the Wellcome Sanger Institute in Cambridge, said that platinum-based chemotherapy remains an effective and often life-saving treatment for children with cancer and that equally effective alternatives are lacking.
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