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Scientists find two routes to mouth cancer

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by Cancer Research UK | News

1 August 2006

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Cancer Research UK scientists have discovered mouth cancer can develop along two distinct pathways, an aggressive or less aggressive route, reveals a study published in Cancer Research* today (Tuesday).

The research lays the foundations for further studies that could help to improve the management of pre-cancerous lesions and possibly prevent the development of the disease in the future. The researchers from Cancer Research UK’s Beatson Institute for Cancer Research in Glasgow took samples from the mouths of 19 people with pre-cancerous lesions, or spots, 16 patients with mouth cancer and four normal mouths. They compared these samples, each one made up from thousands of cells, in an attempt to find out if the disease develops in more than one way.

The researchers identified two different routes by which mouth cancer develops, resulting in ‘mortal’ and ‘immortal’ tumour cells when they are grown in the laboratory. ‘Mortal’ and ‘immortal’ cells are genetically very different. ‘Mortal’ cells have a limited lifespan and so will exhaust themselves as they develop into a tumour, being less likely to spread or recur following treatment. ‘Immortal’ cells on the other hand are much more resilient and will keep on dividing, making them more likely to spread and to cause a recurrence – a major characteristic of aggressive disease.

They found that faults in the p53 gene and missing expression of the p16 gene were closely associated with ‘immortal’, aggressive tumours. Importantly, these same changes were also found in pre-cancerous cells, which grew in laboratory cultures as ‘immortal’ cells. When it is working normally, the p53 gene stops damaged cells dividing and should stop cancers growing, which is probably why faults were found in the p53 gene in ‘immortal’ cells rather than in ‘mortal’ ones. The p16 gene helps to control the cell regulation process and can prevent cancer from developing – expression of this was missing from most of the more aggressive mouth cancer cells.

Lead researcher Professor Paul Harrison, from Cancer Research UK’s Beatson Institute, said: “We found that many of the molecular changes found in ‘mortal’ and ‘immortal’ cancers are also found in their respective pre-cancerous lesions, which suggests that mouth cancer forms in different ways.”

Mouth cancer patients often develop a series of pre-cancerous lesions over a number of years, due to damaged DNA frequently caused by prolonged tobacco and alcohol use. Previously scientists thought all mouth cancers developed via a single route – from pre-cancer to mouth cancer as the DNA in mouth cancer cells’ progressively accumulated more damage. This is the first time scientists have established why some types of pre-cancerous lesions are more likely to develop into more aggressive cancers. This could be important because using current tests, it is impossible to predict which pre-cancers will actually develop into cancer.

Professor Harrison goes on to explain: “The data we collected provide strong evidence for the first time that some mouth cancer tumours are more aggressive than others and are therefore linked to poorer patient survival. We hope in the future that these findings will allow us to discover early on who needs urgent treatment and possibly offer new methods of preventing the disease.”

Professor John Toy, medical director at Cancer Research UK, said: “Cases of mouth cancer in the UK have risen by a quarter over the past 10 years so these are valuable findings that will help scientists gain a clearer understanding the ways the disease can develop and progress.

“1,600 people die every year from the disease and Cancer Research UK has launched an awareness campaign ‘Open Up to Mouth Cancer’ to encourage people to spot the early signs of the disease and reduce their risk. The most common indicators of mouth cancer are sores, ulcers, red or white patches and unexplained pain in the mouth or ear. Less common signs include a lump in the neck, a persistent sore throat or difficulty swallowing. If any of these persists for more than three weeks they need to be checked out by a doctor or dentist.”


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