Nov 29, 2008

Science - Scientists shed light on genetics of cancer relapse

London, November 28 (ANI): A study conducted by researchers at St Jude Children's Research Hospital in Memphis, Tennessee, has revealed that cancer cells that cause a type of childhood leukaemia to recur are often already present in patients, when they are first diagnosed with the disease.

Lead researcher Charles Mullighan says that the new discovery may help doctors treat the cancer more efficiently.

Existing treatments cure more than 80 per cent of the patients with acute lymphoblastic leukaemia (ALL), but children who then have a relapse have only a 30 per cent chance of recovering.

With a view to determining why the disease is so deadly if it relapses, Mullighan and his colleagues collected leukaemic white blood cells from 61 children with ALL as they were diagnosed and after they relapsed.

The researchers examined copy-number variations - stretches of DNA that are lost or duplicated - in the two sets of samples, and found that only six per cent of relapses were caused by completely new cancers.

They revealed that in 42 per cent of the patients who relapsed, the cells were direct descendants of those identified at diagnosis.

However, in 52 per cent of the patients, the relapse arose from ancestors of the original cancer cells that were not detected when the patients were initially screened.

The treatment that a patient with ALL receives depends upon the results of genetic tests of their white blood cells and bone marrow, which are used to classify them into risk categories.

However, the latest discovery by the research team goes to show that some patients might be carrying more dangerous types of cancerous cells that go undiagnosed.

"These variants are present at the time of diagnosis - which is a worry because it means you've got to get them at the time of diagnosis, you can't wait until the patient relapses," Nature magazine quoted Mulligan as saying.

He believes that rare variants of the cancerous cells may be identified with the aid of more sensitive detection techniques, so as to improve treatment of the disease.

The magazine also reports that the research team have found many mutations in genes that are not known to make cancers resistant to drugs.

"They are not drug-resistance genes, they are genes that contribute to the vitality or viability of the leukaemic clones," says co-author James Downing, also from St Jude Children's Research Hospital.

The researchers are presently studying whether single amino-acid mutations in classical drug-resistance genes are important in the evolution of the cancer cells. Their original analysis, which looked at long stretches of DNA, would not have picked up these mutations.

They say that they will publish further findings in a forthcoming issue of the New England Journal of Medicine, based on which doctors will be able to predict whether a particular patient's treatment will be successful. (ANI)

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