Genetic Signatures of DNA-Damaging Processes That Lead to Cancer

Researchers from the Wellcome Trust Sanger Institute and collaborating institutions have provided the first comprehensive compendium of mutational processes that drive tumor development. Together, these mutational processes explain most mutations found in 30 of the most common cancer types. This new understanding of cancer development could help in the treatment and prevention of a wide range of cancers. The results of this seminal work were published online in Nature on August 14, 2013. Each mutational process leaves a particular pattern of mutations, an imprint or signature, in the genomes of cancers it has caused. By studying 7,042 genomes of people with the most common forms of cancer, the research team uncovered more than 20 signatures of processes that mutate DNA. For many of the signatures, they also identified the underlying biological process responsible. All cancers are caused by mutations in DNA occurring in cells of the body during a person's lifetime. Although we know that chemicals in tobacco smoke cause mutations in lung cells that lead to lung cancers and ultraviolet light causes mutations in skin cells that lead to skin cancers, we have remarkably little understanding of the biological processes that cause the mutations which are responsible for the development of most cancers. "We have identified the majority of the mutational signatures that explain the genetic development and history of cancers in patients," says Dr. Ludmil Alexandrov first author from the Wellcome Trust Sanger Institute. "We are now beginning to understand the complicated biological processes that occur over time and leave these residual mutational signatures on cancer genomes." All of the cancers contained two or more signatures, reflecting the variety of processes that work together during the development of cancer.
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