Study identifies missed mutation signature in colorectal cancer

A tumor's DNA can look like a record of the damage it has accumulated. Researchers from the University of California San Diego and collaborators have now identified a previously overlooked mutational signature—a recurring pattern of DNA mutations—in colorectal cancer. Mariya Kazachkova and colleagues found it across three independent datasets containing 2,616 tumors.

The pattern was not entirely new to cancer genomics. It had already appeared in large collections of tumor genomes, but researchers had interpreted it as a combination of other, known signatures. A closer analysis found that it did not match the biological processes previously associated with those signatures, separating it as a distinct signal. The work was carried out by Team Mutographs, which studies how mutation patterns relate to cancer development.

The timing adds another clue. The signature appeared relatively late during colorectal tumor development, suggesting that something changes as the tumor grows and causes cancer cells to accumulate a new form of DNA damage or copying error. Tumors carrying the pattern also had more small insertions and deletions—short stretches of DNA added or lost—which can arise during DNA replication and repair.

And so, concretely? Researchers gain a more precise way to investigate what happens inside some colorectal tumors as they evolve. The study therefore adds a clue for investigating the processes that shape colorectal cancer development.

The result is a finding about tumor biology. Its strength is the recurrence of the pattern across 2,616 tumors and independent datasets; the findings provide an additional clue that the pattern may be related to DNA replication and repair.