CRG: Errors made by 'DNA spellchecker’ revealed as important cause of cancer

CRG: Errors made by 'DNA spellchecker’ revealed as important cause of cancer

News from CRG

Cancer is mostly caused by changes in the DNA of our cells that occur during our lifetime rather than those that we inherit from our parents. Identifying the causes of these ‘mutations’ is a difficult challenge because many processes can result in an identical DNA sequence change in a genome. Researchers at the CRG have now identified one of the important mechanisms that causes these mutations as mistakes made by a DNA ‘spellchecker’ that repairs damage in our genomes.

The researchers identified this process by studying clusters of mutations in more than a thousand tumor genomes, meaning that they hunted for mutations that occur close together in the same part of the genome, such that this is highly unlikely to have happened by chance. “Clustered mutations are likely to be generated at the same moment in time, so by looking at several neighboring mutations at once, we can have a better understanding of what has damaged the DNA,” says Fran Supek, first author of the study. 

By studying clusters, the scientists identified nine mutational signatures that were evident in more than 1,000 genomes of tumors from various organs. Their results, which are published in Cell, revealed new major mutation-causing processes, including an unusual case of DNA repair which should normally safeguard the genome from damage, but is sometimes subverted and starts introducing clustered mutations.

More information:
CRG website

Reference article:
Supek, Fran and Lehner, Ben. "Clustered mutation signatures reveal that error-prone DNA repair targets mutations to active genes". Cell. 27 July 2017. DOI: 10.1016/j.cell.2017.07.003