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Genetic mapping reveals origins of cancer

19 August 2013
Appeared in BioNews 718

A team of researchers has comprehensively charted the genetic 'signatures' of processes that drive tumour development for the first time.

Scientists analysed more than 7,000 genomes and found almost five million mutations from the most common cancers. The processes that cause cancer - such as exposure to cigarette smoke - cause certain mutation patterns, described by the researchers as genetic signatures, highlighting the biological pathways involved in tumour development.

'Our map of the events that cause the majority of cancers in humans is an important step to discovering the processes that drive cancer formation', said Dr Serena Nik-Zainal, study author from the Wellcome Trust Sanger Institute. 'Through detailed analysis, we can start to use the overwhelming amounts of information buried deep in the DNA of cancers to our advantage in terms of understanding how and why cancers arise'.

All cancers are caused by somatic mutations in the DNA of cells in the body – that is, mutations that occur during a person's lifetime. The mutational processes identified by this study were able to explain most of the DNA changes found in 30 of the most common cancers.

Signatures were identified for processes that are well understood, such as tobacco smoke causing mutations that lead to lung cancer, and ultraviolet light in skin cancer. Other signatures were for ageing related processes, immune system processes and processes for repairing damaged DNA. However, 12 of the signatures were as yet unexplained.

'We have uncovered the archaeological traces within cancer genomes of the diverse mutational processes that lead to the development of most cancers', said Professor Sir Mike Stratton, Director of the Wellcome Trust Sanger Institute, who led the study. 'This compendium of mutational signatures and the consequent insights into the mutational processes underlying them has profound implications for the understanding of cancer development with potential applications in disease prevention and treatment'.

The team found that in more than half of the cancers studied, tumour development was linked to a group of enzymes, known as APOBECs, which are known to mutate DNA. These enzymes are activated in response to some viral infections to protect cells. The researchers suggested that these signatures may be the result of collateral damage to the genome caused by the activation of the enzymes.

Cancer Research UK welcomed the findings, with chief scientist Professor Nic Jones saying: 'The genetic fingerprints identified in this fascinating and important study identify several new processes driving the development of cancer. Understanding what's causing them could be an extremely important way to get to the bottom of how cancer develops in the first place – and this will lead to new ways to treat and prevent the disease'.

SOURCES & REFERENCES
Cancer's origins revealed
Wellcome Trust Sanger Institute (press release) |  14 August 2013
Gene study uncovers origins of many common cancers
Reuters |  14 August 2013
Milestone study probes cancer origin
BBC News |  14 August 2013
Researchers map genetics of 30 common cancers
NHS Choices |  15 August 2013
Signatures of mutational processes in human cancer
Nature |  14 August 2013
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