Hidden away behind recent media stories about Ukraine, parties, the cost of living and Covid was the announcement of one of the most significant medical breakthroughs for a very long time. Scientists at the University of Cambridge have used DNA data from 12,222 NHS cancer patients to identify “mutational signatures”, a kind of personal record of the causes of each patient’s cancer.
The study of DNA has come a long way. February 28th, 2023, will mark seventy years since Francis Crick burst into The Eagle pub in Bene’t Street, Cambridge, and announced to its patrons – many from the Cavendish Laboratory where he worked with James Watson – that the pair had discovered “the secret of life”. Their discovery of the double helix, deoxyribonucleic acid, or DNA, had been completed that very morning and its applications have changed the world. I had many a fine pub lunch and pint of real ale in The Eagle during the time I worked at an ad. agency in Cambridge, and occasionally in the years following, but nothing so dramatic ever happened while I was supping my beer!
One of the secrets of this new study’s success seems to have been the sheer number of whole-genome-sequenced cancers that were investigated, significantly more than in previous similar studies. The scientists identified patterns in the DNA of specific cancers, common characteristics which provide them with a complete picture of the mutations which have taken place and contributed to the production of particular cancers.
These “mutational signatures” give insights into whether environmental factors such as smoking or UV light, have triggered the mutations which caused the cancer or whether its appearance is purely a result of internal factors. The method lays out a personal record of the damage suffered by the body and the repairs it has made.
So researchers are now able to understand the underlying mutations generated by different kinds of cancers and the way they operate in the body. Utilising a digital tool called FitMS (the Signature Fit Multi-Step algorithm), they identified 58 new mutational signatures. Such signatures can be compared with existing data to isolate specific characteristics and look for commonalities and differences.
The main author of the study, Professor Serena Nik-Zainal from Cambridge University Hospitals (CUH) and the University of Cambridge, has described these signatures as being “like fingerprints at a crime scene”. Knowing how cancers exhibiting such mutation patterns have been treated previously – and what results have been achieved – will help the scientists build an increasingly detailed picture of the causes of more and more cancers and what drugs or other interventions should be used.
My guess is that this research will lead to a rapid increase in the development of new cancer treatments. Just like the time when Francis Crick piled into The Eagle, so another door has been opened into a new era of scientific analysis and understanding.