Cancer code offers hope of treatment decades early

Cancers could be diagnosed and treated decades before symptoms appear after a landmark study that reveals the genetic errors behind the disease.

The research suggests that cancers that strike late in adulthood can be predicted through DNA mutations that appear as early as childhood.

Certain types of tumour, including ovarian cancer and an aggressive type of brain cancer, could ultimately be identified – and perhaps eradicated – long before patients fall ill, the scientists behind the work said this week.

The findings, which involved 1300 researchers, were the culmination of a decade-long collaboration that explored the entire cancer genome. Screening for the disease will not change immediately but the results promise to help to shape research for a generation.

The study could allow the creation of drugs that would kill cancer at its earliest stage. It could also lead to the creation of tests that would identify the disease years before present methods.

‘‘For more than 30 cancers, we now know what specific genetic changes are likely to happen, and when these are likely to take place,’’ said Dr Peter Van Loo, of the Cancer Genomics Laboratory at the Francis Crick Institute in London, a coauthor of one of 22 scientific papers published on Wednesday from the project. The results could widen the opportunity for diagnosis and treatment, he added.

The Pan-Cancer Analysis of Whole Genomes Consortium project involved researchers from 37 countries. They looked at 47 million genetic changes in more than 2500 human tumours, across 38 types of cancer. The DNA of the tumours – their genomes – were compared with those of healthy cells from the same individuals.

DNA errors occur when cells grow and divide and most of these changes are benign. Crucially, though, the researchers identified a limited number of errors – known as ‘‘driver mutations’’ – that were shared between tumours and gave rise to cancer. Of the early mutations, half involve the same nine genes. This suggests that a small number of genes are common contributors to early cancer development.

By examining how many times errors had been replicated and copied, the researchers were also able to calculate the order in which the changes had happened. About a fifth of the mutations appear to take place early in a tumour’s development. Some of these changes take place years, even decades, before the cancer is found.

Clemency Jolly, of the Crick Institute, said: ‘‘What’s extraordinary is how some of the genetic changes appear to have occurred many years before diagnosis, long before any other signs that a cancer may develop, and perhaps even in apparently normal tissue.’’

In the future a sample of a patient’s blood – which contains fragments of DNA from cells from across the body – could be analysed to look for evidence of these dangerous mutations, Dr Van Loo said. These kinds of clinical applications are likely to be between 10 and 20 years away, he added.

Cancer types in which mutations tend to happen early include ovarian cancer and two types of brain tumour – glioblastoma and medulloblastoma. In the case of glioblastoma, usually detected after middle age, there are likely to be genetic mutations in brain cells during childhood, Dr Van Loo said.

In ovarian cancer, telltale genetic warning signs appear to emerge a decade before diagnosis and sometimes earlier. Pancreatic neuroendocrine cancer also appears to be give itself away early, with a number of chromosomes being deleted in the initial stages.

Many known causes of cancer, such as tobacco smoking, leave a specific fingerprint of damage in the DNA, known as a mutational signature. These fingerprints can help to explain how cancers develop.

In Britain a cancer diagnosis takes place every two minutes, with 363,000 new cases every year, according to Cancer Research UK. The disease causes about 165,000 deaths annually.

Dr Ludmil Alexandrov, of the University of California San Diego, said that the study had described ‘‘mutational signatures in much more detail than before, and we are confident that we now know most of the signatures’’.