THE theory that tumours often occur when the p53 gene is damaged may be flawed, say researchers at the Roswell Park Cancer Institute in Buffalo, New York. The p53 gene has been dubbed 鈥渢he guardian of the genome鈥� because of its presumed ability to spot mutated DNA in cells and destroy them before they can turn cancerous.
Damage to p53 was thought to be a main reason for the development of around half of all cancers, including cancer of the colon. According to the theory, cells become riddled with mutations as soon as p53 is no longer functioning as a guardian.
But research by Garth Anderson and his colleagues at the institute has turned the theory on its head. The scientists set out to discover whether the cells with the heaviest genetic damage were those in which p53 was defective. They examined tumour tissue from 58 patients with cancer of the colon, comparing patterns of DNA in cancerous and healthy cells in each patient. They were shocked to find that p53 seemed to be powerless to prevent catastrophic damage. 鈥淭he cells with the least damage to their DNA had a defective p53 gene. Conversely, the cells with the most damage had normal, functioning p53,鈥� says Anderson.
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The team, whose findings are due to appear next week in the Journal of the National Cancer Institute, has traced another gene which they think precipitates the damage by wrecking DNA. 鈥淭he cell takes the broken DNA and starts gluing it back together again, but in a haphazard way that scrambles the genetic information,鈥� says Anderson. He plans to name the gene suspected of this anarchic jumbling, a phenomenon known as 鈥済enetic instability鈥�, in a future paper.
Anderson still believes that p53 plays an important role in the development of cancer. But he suspects that the theory may have been too readily accepted too soon, luring researchers down blind alleys. 鈥淚 think there鈥檚 been a bandwagon effect to chase mutated p53 as the driver of genetic instability,鈥� he says.
David Lane, a pioneer of research on p53 at the University of Dundee, says that Anderson鈥檚 findings are very interesting but are far from being the last word on p53. 鈥淗e鈥檚 saying there are other mechanisms in tumour formation, and I wouldn鈥檛 disagree with that,鈥� says Lane. 鈥淏ut there鈥檚 a huge amount of evidence lending strong support to the theory that p53 plays a critical role in many cancers.鈥�