Errors made by ‘DNA spellchecker’ revealed as important cause of cancer

Source: MedicalXpress, July 2017

Cancer is mostly caused by changes in the DNA of our cells that occur over a lifetime rather than inherited traits. Identifying the causes of these mutations is a difficult challenge because many processes can result in a DNA sequence change. Researchers at the Centre for Genomic Regulation (CRG) in Barcelona, Spain, have now identified an important mechanism causing these mutations: mistakes made by a DNA ‘spell checker’ that repairs damage in the genome.

The researchers identified this process by studying clusters of mutations in more than a thousand tumor genomes, hunting for mutations that occur close together in the same part of the genome, which are highly unlikely to have happened by chance. The goal was to get a better picture of the mutagenic factors that affect human cells and that might cause cancer.

“Clustered mutations are likely to be generated at the same moment in time, so by looking at several neighboring mutations at once, we can gain a better understanding of what has damaged the DNA," says Fran Supek, first author of the study at the CRG. “Like when police study a pattern of recurrent crimes in order to find a serial killer, here, we show that focusing on patterns of clustered mutations and using a large number of cancer genomes, we can identify the culprits that cause mutations in tumors," he explains.