Asian Scientist (Aug. 15, 2013) – An international team of scientists has described the mutational processes that drive tumor development in 30 of the most common cancer types. This new understanding of cancer development could help to treat and prevent a wide-range of cancers.
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.
Because each mutational process leaves a particular pattern of mutations, a signature, in the genomes of cancers it has caused, scientists can gain insight into these processes by identifying such signatures.
In the study, published in Nature, the scientists studied 7,042 genomes of people with the most common forms of cancer and uncovered more than 21 signatures of processes that mutate DNA.
For many of the signatures, they also identified the underlying biological process responsible.
“We have identified the majority of the mutational signatures that explain the genetic development and history of cancers in patients,” says Ludmil Alexandrov, the lead author of the study.
“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.
However, different cancers have different numbers of mutational processes. For example, two mutational processes underlie the development of ovarian cancer, while six mutational processes underlie the development of liver cancer.
Some of the mutational signatures are found in multiple cancer types, while others are confined to a single cancer type.
Out of the 30 cancer types, 25 had signatures arising from age-related mutational processes.
The team also found that a family of enzymes, which is known to “edit” (in effect mutate) DNA, was linked to more than half of the cancer types.
These enzymes, known as APOBECs, can be activated in response to viral infections. It may be that the resulting signatures are collateral damage on the human genome caused by the enzymes’ actions to protect cells from viruses.
The research team had also recently described a remarkable pattern of mutation in breast cancer whereby small regions of the genome are deluged with mutations. They now show that this process, known as kataegis, is present in most cancers. Researchers speculate that the onset of kataegis may also be linked to the activation of APOBEC enzymes.
The article can be found at: Alexandrov et al. (2013) Signatures Of Mutational Processes In Human Cancer.
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Source: Wellcome Trust Sanger Institute.
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