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Cancer research: Studying gene mutations in sets

 
  Saturday, 05 l 02 l 2011  Source: The Straits Times   
By: Grace Chua
     
 

SCIENTISTS have long studied individual genetic mutations and the increased cancer risks each poses. But researchers are now, for the first time, looking at whole sets of genes in various types of cancers. What does that mean for patients? One day, cancer patients may be screened to find out what sets of genes are mutated. They could then be offered drug therapies specifically targeting the processes that have gone wrong to cause cancer. 

Two research studies here have looked at the genetics of gastric and kidney cancer, which are among the most common cancers in Asia. They found that specific sets of mutations are linked to some types of cancer. But will these findings help patients lead healthier, longer lives? Scientists say they can, if they lead to new drugs or diagnostics. This month, a study on kidney cancer by the National Cancer Centre Singapore and international collaborators found a mutation on a gene called PBRM1 in a third of clear cell renal carcinomas – a cancer type which accounts for about seven in 10 cases of kidney cancer. 

The researchers think the mutation may help solve a kidney cancer mystery. Researchers already know that a gene called VHL is linked to this type of cancer. VHL would normally prevent the growth of blood vessels that feed a burgeoning tumour, but in cancer patients it is often mutated, which stops it from carrying out this function. Instead, the cancer has to be treated with drugs which cut off the growth of those blood vessels. But after about a year and a half of drug treatment, many patients seem to become resistant to the drugs, and the blood vessels grow back. 

“We’re hoping that PBRM1 is related to the cancer cells themselves,” said National Cancer Centre researcher Teh Bin Tean, who also holds a post at the Van Andel Research Institute in Michigan. The gene is known to help regulate the expression of many other genes, so the next step, he added, is to figure out how it interacts with VHL and other related genes. The hope is that researchers could one day find a way to somehow target the cancer directly or prevent drug resistance. Professor Teh’s study was published in the journal Nature. In a separate study published in the journal Cancer Research last November, Prof Teh also examined the group of genes in gastric cancer that is responsible for the “conversations” going on inside a cell. 

The cell does this by using proteins called kinases. These have previously been studied only one by one. But Prof Teh’s study instead looked at groups of them – called kinomes – to figure out where the mutations are and how they add up. He was working with colleagues Patrick Tan from the National University of Singapore’s Cancer Science Institute and Steve Rozen from the Duke-NUS Graduate Medical School. The team is now trying to find out how common – or rare – various sets of mutations are in actual cancer patients.