Researchers from University of California San Diego and their collaborators have discovered a previously unrecognized pattern of DNA mutations in colorectal cancer. These patterns, referred to as mutational signatures, are utilized by scientists to explore the biological and environmental factors that have caused DNA damage throughout cancer progression.
Although this specific pattern had been noted in extensive cancer-genome datasets previously, it was thought to be a combination of already identified mutation patterns. Upon closer examination, the researchers determined that the pattern did not correlate with the known processes it was previously linked to. They observed this same pattern in three independent colorectal cancer datasets that included 2,616 tumors, suggesting that it is a legitimate and recurring characteristic in certain colorectal cancers.
The mutation pattern appears to emerge relatively late in the development of colorectal tumors. This indicates that changes may occur during tumor progression that lead cancer cells to acquire a novel type of DNA damage or replication error.
Additionally, the researchers found that tumors exhibiting this newly identified pattern had a higher frequency of small insertions and deletions in their DNA. Since such insertions and deletions typically occur during DNA replication and repair, this finding offers further insight that the newly recognized pattern may be linked to these biological processes.
More broadly, this study tackles a significant challenge in cancer genomics: understanding what unusual mutational patterns can divulge about the mechanisms that influence cancer progression. This research was conducted by Team Mutographs, funded by Cancer Grand Challenges (CGC). Mutographs aims to tackle the pivotal question concerning the relationship between mutational signatures and cancer progression. The results provide a foundation for Team CAUSE, a newly established CGC team led by the study’s senior author Ludmil Alexandrov, PhD, a professor of cellular and molecular medicine and bioengineering at University of California San Diego and a member of the Moores Cancer Center, which will expand on these findings to uncover the underlying mechanisms that drive these and other unexplained mutational signatures in cancer.
Title: Identification and validation of a previously missed mutational signature in colorectal cancer
Authors: Mariya Kazachkova, Burçak Otlu, Marcos Díaz-Gay, Ammal Abbasi, Sarah Moody, Zichen Jiang, Sandra Perdomo, David C. Wedge, Paul Brennan, Michael R. Stratton, and Ludmil B. Alexandrov
Read the Full Article on Nature Communications
Other posts about University of California San Diego on OncoDaily.
