Research has identified 21 distinctive genetic signatures accounting for 97% of the mutations in the most common cancers.
The international group of researchers led by the Wellcome Trust Sanger Institute examined the genomes from more than 7,000 samples of the 30 most common cancers, comprising almost five million distinct mutations. They identified 21 genome-wide ‘mutational signatures’ proposed to represent distinct mutational processes; all cancers contained at least two signatures, others more than two, and some signatures were common to many different types of cancer.
This includes a signature attributed to the APOBEC family of cytidine deaminase enzymes, which can be activated via immune responses to viral infections, leading the scientists to postulate that these protective actions may simultaneously damage human DNA and make cancer development more likely.
Specific signatures were linked to age, defective DNA maintenance and repair, or exposures known to cause DNA mutation; the biological processes driving other signatures are presently unknown, but researchers are hoping that knowing the mutational pathway will help shed light on potential causes and processes in cancer formation.
In addition to the genome-wide signatures of mutation, small regions subject to high levels of mutation were also identified. These areas are formed by a process termed kataegis previously described in breast cancer, and were found in this study in a large proportion of breast, pancreatic, lung and forms of blood (haematological) cancers. It is suggested that the APOBEC enzymes may also be involved in kataegis.
Comment: Improvements in the diagnosis, prognosis, treatment and indeed prevention of cancer rely on understanding of the processes by which individual cancers form and develop. This research provides a valuable new line of investigation that could add significantly to current knowledge.