Largest-ever study uncovers patterns of mutations that might pinpoint cancer’s causes.
In the new study, the team analysed more than 12,000 cancer genomes collected by the UK National Health Service as part of the Genomics England 100,000 Genomes Project. The researchers then used previously published data sets to verify their findings. This involved developing new analytical tools and an algorithm capable of handling hundreds of thousands of mutations, says Andrea Degasperi, a computational biologist at the University of Cambridge and a co- author on the study.
The work — which included samples from 19 tumour types — yielded dozens of previously unknown mutational footprints, some of which could be traced back to defects in specific cellular methods for repairing DNA. Researchers have probably now found all of the most common mutational signatures, says Dávid Szüts, a cancer biologist at the Research Centre for Natural Sciences in Budapest. “It seems unlikely that the major processes are missed at this point,” he says. But the hunt for rare signatures that occur in less than 1% of tumours in a given organ will probably continue as cancer-genome projects flourish worldwide.
In addition to searching for further mutational signatures, Degasperi hopes to be able to track down the origins of the more mysterious ones that have not yet been linked to a cancer-causing event. He also wants to investigate other kinds of genetic change: the current study focuses on changes to between one and three DNA letters, but DNA sequences can also be deleted, inserted or rearranged in larger chunks.
The hope is that these studies will eventually lead to cancer treatments that are tailored to individual people, he says. “When you understand the mechanism, you might understand a possible correlation with a drug.”