A study has opened the way for a new generation of drugs to combat the genes that give rise to the growth// of cancer tumors.
Scientists have carried out the widest survey yet of the genetic errors that causes tumors to grow. The findings will be used to design anti-cancer drugs targeted at counteracting mutations in a patient's DNA.
All cancers are thought to result from an accumulation of mutations in one or another of the 30,000 genes in the human genome. These mutations cause a cell to multiply uncontrollably to form a tumor that can then spread to other parts of the body.
Scientists have identified about 350 genes that have been implicated in the development of different cancers but, until now, have not had a clear idea about how many mutations in these genes were directly involved in triggering cancer.
The latest study analyzed 200 samples of cancerous tissue, surveying 500 genes and sequencing more than 250 million letters of the DNA code. An international team of more than 60 scientists led by Michael Stratton of the Wellcome Trust Sanger Institute in Cambridge identified 158 mutations in 120 genes that they believe can be implicated in cancer development.
Professor Stratton said the number of mutations that appear to be involved in driving the growth of cancerous tumors was larger than expected, but ultimately the technique will allow scientists to acquire a complete catalogue of all the mutations involved in each class of cancer.
"The human genome is a vast place and this, our first systematic exploration in cancer, has thrown up many surprises," said Professor Stratton. "We have found a much larger number of mutated driver genes produced by a wider range of forces than we expected. It's important because the more cancer genes we find, the more targets we'll have in terms of potential new drugs."
The study, published in the journal Nature, compared the genetic sequence of
the DNA derived from a patient's tumor cells with the DNA of healthy cells from the same patient. The aim was to find the mutations that are present only in the tumor cells, and which could be implicated in their growth.
The scientists concentrated on a class of gene called the kinases, which are known to play a role in cancer. They identified about 1,000 mutations in these genes. The next stage was to try to assess whether these mutations were directly involved in "driving" cancer development, or whether they were harmless "passenger" mutations, which accumulate in the body with age.
Andrew Futreal, a senior team member at the Sanger, said some 158 driver mutations were identified in 120 of the kinase genes studied by the scientists.
"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," said Dr Futreal. "This suggests that many more genes contribute to cancer development than was thought.
"This study vindicates all of the effort that went into the Human Genome Project. Understanding the mutations that cause cancer is crucial in order to develop accurately targeted treatments," said Mark Walport, director of the Wellcome Trust.
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