More Gene Mutations Drive Cancer Than Previously Thought

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Main Category: Genetics
Also Included In: Cancer / Oncology
Article Date: 08 Mar 2007 - 8:00 PDT

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Scientists surveying the human genome have found that many more gene mutations drive the development of cancer than previously thought.

The survey is reported in the journal Nature.

In the largest survey of its kind, an international team comprising over 60 scientists from the UK, Hong Kong, the Netherlands, Belgium, USA and Australia, working for the Cancer Genome Project, examined more than 500 genes and 200 cancers and sequenced more than 250 million letters of DNA code.

They found about 120 new genes that drive the development of cancer cells.

All cancers are thought to be caused by gene mutations. Genes control the behaviour of cells, for example they tell them when to divide and when to die; thus abnormal genes either issue faulty instructions or the correct instructions at the wrong time or both, which leads to abnormal cell development and cancer.

Michael Stratton from the Wellcome Trust's Sanger Institute in Cambridge, UK, and one of the survey team leaders said "This is a lot more cancer genes than we expected to find."

The survey also discovered that two types of gene mutation are involved in cancer: driver and passenger. The driver mutations are thought to drive the rampant cell growth that causes cancer, while the passenger ones, which exist in much larger numbers, just go along for the ride.

Of the 1,000 cancer-specific mutations found, the team believes that about 150 of them are driver genes.

It is not easy to spot the difference between a driver and passenger gene, something this survey suggests will pose a great challenge for scientists.

Dr Andy Futreal, co-leader of the Cancer Genome Project explained "It turns out that most mutations in cancers are passengers."

"However, buried amongst them are much larger numbers of driver mutations than was previously anticipated. This suggests that many more genes contribute to cancer development than was thought," he added.

The types of genes that Futreal and his colleagues investigated are known as kinase genes. They have been linked with cancer development before. These protein genes act like relays, switching different types of cell behaviour on and off.

One example of a kinase gene is the BRAF, which an earlier study showed to be mutated in 60 per cent of malignant melanomas. This led to the development of new drugs, now in clinical trials, to treat melanoma.

This broader survey covered a wider range of the more common types of cancer, including breast, lung, colorectal and stomach cancers.

The researchers also found that a particular group of kinase genes "involved in the Fibroblast Growth Factor Receptor signalling pathway was hit much more than we expected, particularly in colorectal cancers," said Dr Futreal.

The survey also showed that buried inside each mutation are important coded messages, and that the type of mutation varied widely between different cancer types. This suggests that in some cases the process of mutation begins decades before the cancer presents itself.

It is as though gene mutations are "archeological sites" where written inside the DNA of each cell is a historical coded pattern that reveals the original cause of the cancer. In some cases the code can be deciphered, for instance damage from UV radiation or sunlight, or carcinogens in tobacco smoke, but in other cases the code is too hard to crack, which means more research effort is needed to unravel their mysteries.

"This study vindicates all of the effort that went into the Human Genome Project," said Dr Mark Walport, Director of the Wellcome Trust, the largest independent charity in the UK and the second largest medical research charity in the world, and the sponsors of the survey.

"Understanding the mutations that cause cancer is crucial in order to develop accurately targeted treatments," added Dr Walport.

"Patterns of somatic mutation in human cancer genomes."
Christopher Greenman, Philip Stephens, Raffaella Smith, Gillian L. Dalgliesh, Christopher Hunter, Graham Bignell, Helen Davies, Jon Teague, Adam Butler, Claire Stevens, Sarah Edkins, Sarah O'Meara, Imre Vastrik, Esther E. Schmidt, Tim Avis, Syd Barthorpe, Gurpreet Bhamra, Gemma Buck, Bhudipa Choudhury, Jody Clements, Jennifer Cole, Ed Dicks, Simon Forbes, Kris Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jon Hinton, Andy Jenkinson, David Jones, Andy Menzies, Tatiana Mironenko, Janet Perry, Keiran Raine, Dave Richardson, Rebecca Shepherd, Alexandra Small, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, Daniel P. Cahill, David N. Louis, Peter Goldstraw, Andrew G. Nicholson, Francis Brasseur, Leendert Looijenga, Barbara L. Weber, Yoke-Eng Chiew, Anna deFazio, Mel F. Greaves, Anthony R. Green, Peter Campbell, Ewan Birney, Douglas F. Easton, Georgia Chenevix-Trench, Min-Han Tan, Sok Kean Khoo, Bin Tean Teh, Siu Tsan Yuen, Suet Yi Leung, Richard Wooster, P. Andrew Futreal and Michael R. Stratton.
Nature 446, 153-158 (8 March 2007)
doi:10.1038/nature05610

Click here for Abstract.

Click here for Catalogue of Somatic Mutations in Cancer, COSMIC (Wellcome Trust, Sanger Institute).

Written by: Catharine Paddock
Writer: Medical News Today
Copyright: Medical News Today
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