Researchers from the Centre for Genomic Regulation in Barcelona, Spain, have discovered that the molecular toolkits that repair our DNA don’t seem to work equally well across the whole genome. Looking at 17 million gene faults across the DNA of 650 cancer patients and publishing their findings in the journal Nature, the scientists discovered that certain parts of the genome where genes are actively being read tend to have more accurate ‘spellchecking’ than the parts where genes are turned off, through a process called mismatch repair. This means that even though mutations are occurring at more or less the same rate throughout the whole genome, mistakes in genes in these lively areas are more likely to be corrected than those elsewhere. Importantly, many of the uncorrected regions seem to contain genes that are implicated in cancer when faulty.
Intriguingly, the team also found differences in patterns of faulty genes in different types of cancer, reflecting underlying differences in patterns of gene activity. And once the DNA spellchecking machinery was turned off in cells, they started picking up mistakes across the whole genome, not just in under-used areas. Faulty mismatch repair is found in several types of cancer, including bowel, stomach and womb cancers, so these findings give new insights into how these tumours might start, or even how they might be treated more effectively in future.