Tumour mutations often misidentified

Genetic testing to guide the choice of cancer treatment may be misleading unless tumour DNA is compared to normal DNA, a study has found.

The researchers found that around two-thirds of mutations in cancerous tumours are also found in normal tissue, suggesting that these mutations are not directly related to the cancer.

'Increasingly, hospitals and companies are beginning to sequence patients' tumors in an attempt to personalise therapy. However, many are not sequencing each person's normal tissue to filter out non-cancer-related changes and to really understand what is occurring in the tumour,' said Dr Victor Velculescu of Johns Hopkins University School of Medicine in Baltimore, USA, who led the study.

The researchers sequenced and analysed DNA from 815 people with advanced cancers, taking two samples from each patient: one from the tumour and one from normal tissue. 

The team used two tests. The first, which looked for mutations in all genes in the genome, showed that 65 percent of all the mutations found in tumour DNA were also found in normal DNA.

The second detected mutations only in the 111 genes that are most likely to be involved in cancer. With this test, 30 percent of mutations in cancer cells were also detected in normal cells, which therefore would be false-positive results if the tumour alone had been screened. 

The findings come at a time when drug companies are increasingly focused on developing drugs that target specific mutations. But Dr Velculescu says their findings suggest that this could come at the expense of patients.

'There is a rush to do this clinically and apply it to patient treatment without thinking about what the best control is,' Dr Velculescu told Nature. 'You could use that information to place patients on inappropriate therapy.'

Dr Michael Berger, a cancer researcher at Memorial Sloan Kettering Cancer Center in New York told Nature that a programme at his organisation has sequenced both normal and tumour tissue of cancer patients.

Although useful, Berger notes that the extra sequencing costs more money and requires more patient counselling. Mutations in normal tissue may be related to genetic diseases, so patients also need to consider the implications of these additional tests for family members.

However, he remarks: 'Sequencing unmatched tumours is better than not sequencing at all.'