Researchers identified a distinct mutational signature in colorectal cancer that previous genomic analyses had missed, according to a study published in Nature Communications. The signature, named SBS_D, appeared consistently across an evaluation of 2,616 colorectal cancers drawn from three independent patient cohorts.
The team re-evaluated earlier work on 802 microsatellite-stable colorectal cancers where SBS_D had initially been decomposed into the known signature SBS18. The new evaluation showed that SBS_D represents a separate biological process. While its pattern resembles signatures linked to DNA repair deficiencies, the researchers found no evidence that canonical defects in those repair pathways cause it. Instead, the authors proposed that the signature arises from DNA repair infidelity developing late in tumor progression within DNA repair-proficient tumors.
The researchers submitted SBS_D to the COSMIC database, which assigned it the provisional designation SBS111. The study utilized genomic data generated in part by the TCGA Research Network and ran computational workloads on the Triton Shared Computing Cluster at the San Diego Supercomputer Center of the University of California San Diego.
Mariya Kazachkova and Ludmil B. Alexandrov of UC San Diego authored the study alongside collaborators from the Wellcome Sanger Institute, the International Agency for Research on Cancer, and the University of Manchester. The research received support through the Cancer Grand Challenges Mutographs team funded by Cancer Research UK, alongside grants from the US National Institutes of Health.
