Many gene mutations drive cancer


Mar 7, 2007

The number of mutated genes that drive the development of cancer is greater than had been thought, research shows.

However, as well as these "driver" mutations, each type of cancer cell carries many more "passenger" mutations which play no role in causing disease.

The findings, published in Nature, come from the most extensive analysis yet of the human genome and cancer.

Sanger Institute scientists looked at more than 500 human genes and 200 types of cancer.

The research suggests that cancer biologists will face a big challenge in distinguishing between mutations that cause cancer and those that do not.

Professor Mike Stratton, co-leader of the Cancer Genome Project, said: "We have found a much larger number of mutated driver genes produced by a wider range of forces than we expected."

The researchers studied genes of a type called kinases, some of which have been previously implicated in causing cancers.

Cell switches

Kinases act as switches within cells, controlling behaviour such as cell division. In mutated forms this process can go awry, leading to the uncontrolled division of cells characteristic of cancer.

One example is the BRAF gene, which is mutated in more than 60% of cases of the skin cancer malignant melanoma.

The Sanger team identified possible driver mutations in 120 genes, most of which had not been seen before.

However, most mutations were found to be of the harmless "passenger" type.

The team also found the type of mutation varied markedly between individual cancers - and that some of the processes that generated them were active decades before the cancer showed itself.

The latest analysis was made possible by Sanger's work in decoding around a third of the entire human genome.

Dr Mark Walport, director of the Wellcome Trust, which funds the Sanger Institute, said the study showed how important the Human Genome Project had been.

He said: "Understanding the mutations that cause cancer is crucial in order to develop accurately targeted treatments."

Dr Francis Collins, director of the National Human Genome Research Institute in the US, said powerful analytical tools were now available to probe the mysteries of cancer.

He said: "The important and interesting data on protein kinases in this report further encourages the conclusion that a full assault on the cancer genome will yield many opportunities to revolutionise diagnosis and treatment."