Mutations in “Guardian of the Genome” Assist Cancer in Spreading
Tumours are helped in their development by mutating the most important cancer-prevention gene, p53, scientists from Melbourne have found. The study, published in Genes and Development, found that mutant p53 prevents the regular p53 protein from activating its natural defences, increasing the risk of the cancer spreading.
Known as the ‘guardian of the genome’ for its property of protecting cells from cancer, two copies of the p53 gene are normally found in every cell. Defective p53 is found in around half of all human cancers.
The Melbourne team found that during early cancer development, one of the p53 copies can undergo a sudden mutation, which leads it to block the still-normal p53 from engaging in protective activities like DNA repair.
The team is now looking at whether the mutant p53 protein acts in the same way in established tumours. One of the researchers, Dr Gemma Kelly, said this could have important implications for drug treatment: “If mutant p53 acts by tackling normal p53, then it may no longer play a role in established tumours where no normal p53 is produced. This would mean that drugs that block mutant p53 would have no clinical benefit.
“Conversely, if mutant p53 has new, cancer-promoting activities of its own in established tumours, then a drug that specifically blocks mutant p53 could be beneficial for treating thousands of patients.”