“The only way we can fully understand the impact of cancer across a lifetime, particularly in the later stages when treatments often stop working, is by analysing tumour samples after people have died,” says Mariam Jamal-Hanjani, chief investigator on the study and an Associate Researcher at the Crick.
A recent analysis of data from 22 participants in PEACE has now revealed unexpected ‘mutational fingerprints’ in healthy organs of people with advanced cancer, a discovery that is advancing our understanding of how cancer and its treatments affect the body.
By reading the DNA sequences in these healthy tissue samples, Crick postdoctoral research scientist Oriol Pich identified previously unseen patterns of mutations across multiple organs. He and the team then matched these genetic readouts to clinical data from individuals, including details of their treatments and lifestyle factors such as whether they smoked.
“We expected to see many mutations from risk factors like drinking alcohol and smoking in samples from the liver and lungs,” describes Oriol. “But our analysis also showed that some types of cancer treatment produce bursts of mutations in other healthy tissues and organs.”
Surprisingly, they found genetic changes associated with immunotherapy – a treatment not thought to directly damage DNA. The researchers believe this may be explained by the way immunotherapy places selective pressure on cells, allowing certain mutated populations to grow.
The team also found higher-than-expected levels of mutations in organs such as the spleen, raising new questions about how different parts of the body respond to cancer and its treatment.
While not all these mutations would have led to future cancers, the findings highlight the broader impact of cancer treatment on the body, and underline the need for therapies that are more targeted and less harmful to healthy cells.
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