DNA analysis of tumors reveals a ‘treasurehouse’ of clues to the causes of cancer


DNA analysis of thousands of tumors from NHS patients has found a ‘treasure trove’ of clues to the causes of cancer, with genetic mutations providing a personal history of the damage and repair processes each patient has gone through.

In the largest study of its kind, a team of scientists led by Professor Serena Nik-Zainal from Cambridge University Hospitals (CUH) and the University of Cambridge, analyzed the complete genetic makeup or whole genome sequences of over 12,000 NHS cancer patients. .

Due to the large amount of data provided by whole genome sequencing, researchers have been able to detect patterns in cancer DNA – or “mutational signatures” – that provide clues as to whether a patient has ever been exposed. to environmental causes of cancer such as smoking or UV light, or has internal cellular dysfunctions.

The team was also able to spot 58 new mutational signatures, suggesting that there are other causes of cancer that we don’t yet fully understand.

This research was supported by Cancer Research UK and published today in the journal Science. The genomic data was provided by the 100,000 Genomes Project, an England-wide clinical research initiative to sequence 100,000 whole genomes from around 85,000 rare disease or cancer patients.

Dr Andrea Degasperi, a research associate at the University of Cambridge and first author, said: “Whole genome sequencing gives us a complete picture of all the mutations that have contributed to each person’s cancer. With thousands of mutations per cancer, we have unprecedented power to search for commonalities and differences between NHS patients, and in doing so we have discovered 58 new mutational signatures and expanded our knowledge of cancer.

Serena Nik-Zainal, Professor of Genomic Medicine and Bioinformatics at the University of Cambridge and Honorary Consultant in Clinical Genetics at CUH, said: “The reason why identifying mutational signatures is important is that they are like fingerprints at a crime scene – these help identify the culprits of cancer. of Achilles’ in individual cancers.

“We were able to carry out forensic analysis of over 12,000 NHS cancer genomes thanks to the generous contribution of patient and clinician samples from across England. We also created FitMS, a computational tool to help scientists and clinicians identify old and new mutations. signatures in cancer patients, to potentially more effectively inform cancer management.”

This study shows how powerful whole genome sequencing tests can be in giving clues about how cancer may have developed, how it will behave and what treatment options would work best. It is fantastic that the knowledge gained from the NHS 100,000 Genomes project can potentially be used within the NHS to improve the treatment and care of people with cancer. »

Michelle Mitchell, Chief Executive of Cancer Research UK

Professor Matt Brown, Scientific Director of Genomics England, said: “Mutational signatures are an example of using the full potential of WGS. We hope to use the mutational indices observed in this study and reapply them to our patient population, with the ultimate goal of improving the diagnosis and management of cancer patients.”


Journal reference:

Degasperi, A. et al. (2022) Surrogate Mutational Signatures in Whole Genome Sequenced Cancers in the UK Population. Science. doi.org/10.1126/science.abl9283.

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