The research, by scientists at the University of Cambridge and King’s College London, uncovered the patterns of DNA damage caused by 41 environmental agents, such as ultraviolet light, tobacco smoke and polycyclic hydrocarbons. The human genome is made up of nucleotides represented by the letters A, C, G and T. Mutations in the sequence of these letters such as when an A becomes a G, for example can be caused by multiple factors, including environmental ones.
Mutations in the sequence
These are copied when cells divide and reproduce, and over time the number of errors accumulates; leading to uncontrolled cell growth the development of tumours. Researchers can now detect the patterns, or mutational signatures; therefore in these tumours. Dr Serena Nik-Zainal from the Department of Medical Genetics and MRC Cancer Unit; who led the Cambridge team, said: “Mutational signatures are the fingerprints that carcinogens leave behind on our DNA; and just like fingerprints, each one is unique.
“They allow us to treat tumours as a crime scene and, like forensic scientists; allow us to identify the culprit – and their accomplices responsible for the tumour.” Because To study this, the researchers use induced pluripotent stem cells, which are skin cells that have been reprogrammed to return to their original; master cell state.
Exposing them to 79 known or suspected environmental carcinogens; they examined them using whole genome sequencing and found 41 had left a characteristic fingerprint on the DNA. Professor David Phillips, who led the King’s College London team, said: “We’ve used this technique to create the most comprehensive catalogue to date of the patterns of DNA damage produced by environmental agents across the whole human genome.
“It should allow us to examine a patient’s tumour and identify some of the carcinogens they have been expose to that may have cause the cancer.” Because Exploring individual chemicals found in tobacco smoke; they identified; for the first time; which ones caused signatures like those found in the lung cancer of patients who smoked.
Some dietary chemicals
They also identify fingerprints left by common chemotherapy drugs; therefore some dietary chemicals and some present in diesel exhaust fumes. The teams hope to expand the research to develop an encyclopedia of signatures. Dr Nik-Zainal added: “Our reference library will allow doctors in future to identify those culprits responsible for causing cancer.
Such information could be invaluable in helping inform measures to reduce people’s exposure to potentially dangerous carcinogens.” Because The study, published in Cell; is find by a Wellcome Strategic Award, with additional support from Cancer Research UK and the Medical Research Council.