Researchers map genetics of 30 common cancers

Behind the Headlines

Thursday August 15 2013

Researchers looked at nearly five million genetic mutations

"Cancer 'signatures' reveal origins of disease," Sky News reports, explaining how "a team of scientists discover the genetic patterns left by complex processes which mutate DNA and lead to cancer".

This headline is based on research that looked at more than 7,000 cancers to identify "signature" patterns in genetic mutations. These signature patterns suggest how the cancer-causing mutations arise.

Researchers identified almost five million mutations that fell into 21 signature patterns. The causes of some of these signatures were identified. The researchers found that some patterns were related to increasing age, for example, or exposure to tobacco smoke or ultraviolet (UV) light. Other signatures were related to processes not previously linked to cancer-causing mutations.

But the processes that cause some signatures are not yet known. Greater understanding of exactly how the DNA mutations that lead to cancer arise could eventually help researchers develop new ways of treating or preventing the disease.

However, there is still a great deal of work to be done, particularly for the signatures with no known cause. Research analysing which mechanisms produce similar mutation patterns in the lab would be necessary, as well as looking at how the characteristics of the cancer and the person with the cancer relate to the signature.

Overall, the findings offer an intriguing and exciting new avenue of research into what causes cancer.


Where did the story come from?

The study was carried out by a large group of researchers from international centres, including the Wellcome Trust Sanger Institute, and was funded by the Wellcome Trust and other sources.

It was published in the peer-reviewed journal Nature and has been made available on an open access basis, so it is free to read or download.

Many news sources reported this story, with well-balanced coverage.


What kind of research was this?

This was a laboratory study that looked at what we can learn about the origins of cancer from the patterns of genetic mutations found in human cancers.

Cancers arise as a result of changes (mutations) to the DNA in a cell that cause it to divide in an uncontrolled manner. The mutations assessed in this study are not inherited, but develop in the cell during our lifetime.

These mutations can occur in different ways. For example, they can arise when there are problems with how DNA replicates itself when the cell divides, when the DNA is exposed to harmful chemicals or UV light, or when there are defects in how the cell repairs its DNA.

The researchers say that for some cancers we do have some understanding of which processes contribute to the mutations. But for others we don't know how many of these cancers develop.

It is known that different processes associated with the onset of these cancers often occur together, leading to different combinations of mutations called "signatures". The researchers therefore wanted to see if looking at the mutation signatures of different types of cancer could provide evidence about how these cancers arose.


What did the research involve?

The researchers used a computer algorithm they developed to identify mutation signatures in the sequences of DNA extracted from cancer cells.

They did this using DNA data from 7,042 cancers of 30 different types, with DNA from each individual's non-cancerous cells acting as a control.


What were the basic results?

The researchers identified 4.9 million DNA changes in the cancer cells. The average number of mutations varied within each type of cancer. Some childhood cancers showed the fewest mutations, while cancers associated with ongoing mutation-causing exposure, such as lung cancer and malignant melanoma, had the most mutations. These differences were related to the age of the line of cells that developed the cancer.

The researchers identified 22 different mutation signatures. Some of these were found in multiple cancer types. Most cancers showed at least two mutation signatures, with six signatures seen in liver, uterus and stomach cancers. This suggested that some cancers may have more complex mutation-forming processes than others.

The most common signature was found in 60.7% of cancer samples. This pattern became more common with the increasing age of the person with the cancer, and was therefore considered to probably be associated with cell ageing.

Another common type of signature, found in 14.4% of cancers, was considered to possibly be associated with the over-activity of a family of proteins called APOBEC enzymes. These enzymes are involved in DNA replication (a cell copying itself when it divides) and repair, and are also part of the body's defence against viruses.

The researchers say that scientists were unaware that these enzymes could be involved in cancer mutation development.

Other mutation signatures appeared to be associated with BRCA1/2 mutations – genes known to be involved in breast and ovarian cancers – as well as smoking, DNA repair problems, UV light and other causes. However, 12 of the mutation signatures did not have a known or suspected associated cause, so these remain to be investigated.


How did the researchers interpret the results?

The researchers concluded that their results showed the diversity and complexity of the processes leading to cancer-causing mutations.

They say that these findings may have implications for understanding what causes cancer, as well as its prevention and treatment.



This research has identified more than 20 mutation signatures in different cancers. Some of these signatures point to specific causes that are already known to contribute to cancer, such as age and smoking. Other mutations have pointed to processes not previously known to be associated with cancer, while others do not have known processes that cause them.

Greater understanding of exactly how the DNA mutations that lead to cancer arise could eventually help researchers develop new ways of treating and preventing the disease.

However, there is still work to be done. The authors note that further study is needed of the signatures with no known cause. This would include looking at which mechanisms can produce similar patterns of mutations in the lab, and how the characteristics of the cancer and the person with the cancer relate to which signature is present.

Overall, the findings open an intriguing avenue of research into what causes cancer.


Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Genetic map of cancer reveals trails of mutation that lead to disease. The Guardian, August 14 2013

Milestone study probes cancer origin. BBC News, August 14 2013

Revealed: The DNA secrets of 30 common cancers - that could pave the way for new treatments. Daily Mail, August 15 2013

Cancer 'Signatures' Reveal Origins Of Disease. Sky News, August 14 2013

Links to the science

Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. Published online August 14 2013


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