Page last updated at 00:24 GMT, Thursday, 4 March 2004

Unusual DNA may be key to cancer

DNA
DNA is usually a double helix

Researchers have discovered that a weakness in the structure of DNA may make some cells more likely to turn cancerous.

A team from the University of Southern California examined a gene linked to a form of non-Hodgkin's lymphoma.

They found that the gene had a weak point where its DNA was not arranged in the classic double helix structure.

The research, published in Nature, may help give scientists more understanding of how cancer is triggered.

It is important to know how and why cancer begins - and this is an important step to understanding that.
Dr Michael Lieber

The research focused on immune system cells called lymphocytes which fight infection.

The cells carry a gene called Bcl-2 which plays a key role in controlling suicide of cells when they come to the end of their natural lives.

However, if it is too active it can disrupt the suicide process, and trigger the development of a form of non-Hodgkin's lymphoma called follicular lymphoma.

Scientists already knew that the gene's activity was disrupted when the chromosome on which it sits, number 18, breaks, and trades material with another chromosome, number 14.

The USC team examined the weak point on the gene where this break is most likely to happen. This is known as a "fragile site".

Molecular quirk

They found that at this precise point, the DNA was not arranged in the double helix formation so famously discovered by Francis Crick and James Watson in the 1950s.

Lead researcher Dr Michael Lieber said: "Of all the chromosomal fragile sites in cancer, this is the first one where we've actually understood why it's fragile.

"And it is because of this molecular quirk in the Watson-Crick helix.

"It is important to know how and why cancer begins. And this is an important step to understanding that - to understanding why the break is happening and why the chromosomes are swapping arms. "

However, the researches admit they still know little of the exact structure of DNA at this site.

Follicular lymphoma is the second-most common form of non-Hodgkin's lymphoma. The five-year survival rate is around 75%.

Dr Simon Vincent, from Cancer Research UK, said it was known that the DNA in tumour cells can become very mixed up as the chromosomes break and stick back together, disrupting the normal function of the genes on the chromosomes.

"We have know for a while that these breaks are not totally random - they are more likely to happen at some points in our DNA than others.

"However, until now we did not know why this was the case. This work suggests that one of these sites has a different structure from the rest of the DNA.

"If we see these same special structures at other sites involved in cancer it could explain why the DNA in tumours becomes so jumbled."



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