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Last Updated: Monday, 14 February, 2005, 15:48 GMT
Poor cell memory is key to cancer
Changes to DNA govern gene expression
A family of enzymes may trigger cancer by sabotaging cell memory, research suggests.

Every time a cell divides, it has to remember which of its genes are switched on or off at the time.

If that memory is impaired, this can disrupt the proper development of cells and trigger cancer.

Scientists at Cancer Research UK and Cambridge's Babraham Institute have shown certain enzymes can alter this genetic memory.

The mechanism of genetic alteration that this research has uncovered may underlie the molecular basis of a substantial proportion of cancers.
Dr Lesley Walker
Evidence of this interference was present in a large proportion of tumours - strongly implicating the enzymes in the development of cancer.

Retaining the memory of which genes are switched on and which are switched off when a cell divides is called epigenetics.

Often genes are switched off by a change to the structure of its component DNA - a process known as methylation.

The researchers discovered that AID, an enzyme involved in the formation of the immune system, can also alter methylation in DNA.

This could leave cells with inaccurate memories - and lead to cancer.


Researcher Dr Svend Petersen-Mahrt said: "This is the first detailed study to show that the AID enzyme can act on methylated DNA.

"AID chemically alters the methylated DNA by mutating it. Cells have ways to repair such mutations, but in this case, when the cell repairs the DNA, it is left unmethylated and the cell's memory of the gene's 'off' status is lost.

"When AID acts in an uncontrolled fashion on a key gene, this gene will be switched on in the wrong place or at the wrong time.

"This could interfere with the usual control of cells' behaviour, leading to the development of cancerous traits such as uncontrolled growth."

The researchers looked for characteristic alterations in colon cancer genes, and found that in a substantial number of tumours, similar mutations to those caused by AID were present.

Dr Wolf Reik, who also worked on the study, said: "If we can now show that these mutations were caused by AID or other members of that family, it will strongly suggest that these enzymes are a major contributor to the development of cancer."

The study was also the first to find AID in stem cells, suggesting it plays a role in the early stages of development.

It is hoped that work of this kind will eventually enable scientists to turn mature cells back into stem cells which have the ability to become any type tissue in the body.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "The mechanism of genetic alteration that this research has uncovered may underlie the molecular basis of a substantial proportion of cancers.

"Every advance in our understanding of the causes of cancer puts us in a better position to improve ways of detecting and treating the disease."

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