Advanced Genetic Technique Uncovers Hidden Mutations That Can Lead to Cancer

Researchers have enhanced a sophisticated DNA sequencing technology known as NanoSeq, enabling the detection of rare and naturally occurring mutations within healthy human tissues. This breakthrough provides critical insights into the earliest stages of cancer development and how mutations accumulate over time in normal tissues.

In the largest study of its kind, the team applied this improved sequencing method to analyze cheek swabs and blood samples from over 1,000 individuals ranging in age from 21 to 91, including smokers, non-smokers, and people with diverse lifestyle exposures. They identified more than 340,000 mutations in cheek cells alone, over 62,000 of which occurred in genes associated with cancer progression. The study revealed 49 genes under positive selection, indicating that certain mutations confer a growth advantage to cells, with notable mutations found in well-known cancer genes such as TP53.

The research uncovered distinct mutational signatures linked to aging, smoking, and alcohol use. For instance, smoking was associated with increased mutations in the NOTCH1 gene and amplified growth of mutant cell clones, while heavy alcohol consumption left specific DNA change patterns. Despite the prevalence of mutations, most mutated cell clones remained very small and did not grow over time, suggesting natural cellular mechanisms prevent mutated cells from developing into cancer.

This pioneering work demonstrates that utilizing targeted NanoSeq on non-invasive samples allows for detailed mapping of mutation landscapes in healthy tissues, offering potential for early cancer risk assessment and understanding lifestyle contributions to genetic changes. Additionally, the improved NanoSeq technology is now instrumental in broader cancer and human genetics research at the Sanger Institute.

Furthermore, ongoing studies using NanoSeq also explore how mutations in sperm DNA increase with age, which could impact future generations, and help identify environmental and lifestyle factors that influence genetic risk. Scientists involved emphasize that this methodology could become a powerful tool for early detection and preventive strategies in oncology and personalized medicine.

Source: https://medicalxpress.com/news/2025-10-genetic-tool-reveals-hidden-mutations.html