Researchers identify previously overlooked DNA mutation pattern in colorectal cancer

Researchers from the University of California San Diego and collaborators have identified a previously overlooked pattern of DNA mutations in colorectal cancer. The study, published in Nature Communications, was conducted by Team Mutographs, a group investigating the relationship between mutational signatures and cancer development.

Scientists use mutational signatures to investigate the biological and environmental processes that damage DNA during cancer development. This particular pattern had been detected in large cancer-genome data sets before, but researchers had interpreted it as a combination of other, already known mutation patterns.

When the researchers took a closer look, they found that the pattern was not associated with the known processes to which it had been attributed. They validated the signature in three independent colorectal cancer data sets comprising 2,616 tumors, providing evidence that it is a genuine and recurring feature of some colorectal cancers.

The mutation pattern appears relatively late as colorectal tumors develop. This timing suggests that something may change during tumor development that causes cancer cells to accumulate a new type of DNA damage or copying error.

Tumors with the newly recognized pattern also had more small insertions and deletions in their DNA. Because insertions and deletions can arise during DNA replication and repair, this finding provides an additional clue that the pattern may be related to these processes.

The work addresses a fundamental challenge in cancer genomics: determining what unusual mutational patterns can reveal about the processes that shape cancer development. The researchers note that the pattern's late emergence and association with replication-related mutations warrant further investigation into its underlying cause.