Most cells carry the complete genome in their nucleus, and as cells divide and age, they can pick up mutations in their genome. Some mutations are harmless, and others can be repaired, but sometimes, harmful mutations stick around in the genome. If harmful mutations start to build up, or if they occur in certain critical genes, cancer can arise. The more scientists can learn about the mutations that drive cancer, the more likely it is that effective therapeutics can be created to stop cancer from developing or spreading. Scientists have now found more of those cancer-promoting mutations. The findings have been reported in Science.
In this study, researchers used whole-genome sequencing to study cancers that occurred in over 12,000 patients, including primary tumors and metastatic cancers.
The study showed that some mutations can reveal a personalized history of how DNA has been damaged and repaired in one patient, and led to cancer. By sequencing the whole genome of cancerous cells, the researchers identified mutational signatures that could provide insights about the environmental and biological influences on cancer development, such as smoking, UV light exposure, or cellular disruptions. The researchers found 58 novel mutational signatures. They suggested that there may be other causes of cancer we don't know much about yet.
"The reason it is important to identify mutational signatures is because they are like fingerprints at a crime scene - they help to pinpoint cancer culprits. Some mutational signatures have clinical or treatment implications; they can highlight abnormalities that may be targeted with specific drugs or may indicate a potential Achilles heel in individual cancers," said Serena Nik-Zainal, a professor of genomic medicine and bioinformatics at the University of Cambridge.
The investigators also developed a computational tool that researchers and clinicians can use to assess new and old mutational signatures in patients, said Nik-Zainal. The tool is called FitMS, and it could improve the management of cancer cases.
"Mutational signatures are an example of using the full potential of WGS. We hope to use the mutational clues seen in this study and apply them back into our patient population, with the ultimate aim of improving diagnosis and management of cancer patients," added study co-author Professor Matt Brown, chief scientific officer of Genomics England.