Precision medicine - in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers - has advanced to the point where it can now impact the care of a majority of children with brain tumours, a new study by investigators at Dana-Farber/Boston Children's Cancer and Blood Disorders Center suggests.

In the largest clinical study to date of genetic abnormalities in paediatric brain tumours, researchers performed clinical testing on more than 200 tumour samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials.

The findings, reported online today by the journal Neuro-Oncology, demonstrate that testing paediatric brain tumour tissue for genetic abnormalities is clinically feasible and that in many cases the results can guide patients' treatment.

The need for new approaches to treating brain cancer in children is urgent, the study authors say.

"Although there has been a great deal of progress over the past 30 years in improving survival rates for children with cancer, advances in paediatric brain cancer haven't been as dramatic," says co-lead author Pratiti Bandopadhayay, MBBS, PhD, of Dana-Farber/Boston Children's. "In a recent study, brain tumours accounted for 25 percent of all paediatric deaths attributed to cancer. In addition, many of the current therapies can result in long-term difficulties in cognitive or physical functioning."

Since emerging from research labs more than a decade ago, targeted therapies for cancer have significantly improved the treatment of certain types of leukaemia, digestive system tumours, and breast cancer, among other malignancies.

The new study is unique in that it reports on the largest collection of paediatric brain tumours to be genetically profiled as patients came to clinic.

Pathologists and cytogeneticists performed the testing in a federally approved clinical laboratory--certified under Clinical Laboratory Improvement Amendments (CLIA) as the only type of labs in the United States whose findings can guide patient treatment.

Dana-Farber/Boston Children's, the researchers noted, is one of the few centers in the country to regularly analyse the genetics of patients' paediatric brain tumours.

The researchers plumbed the genomes of 203 paediatric brain tumour samples, representing all major subtypes of the disease.

They analysed 117 of the samples with OncoPanel testing, a technology that sequences the exomes - the sections of DNA that hold the blueprints for making specific cell proteins --- for irregularities in 300 cancer-related genes.

They also studied 146 samples tested with OncoCopy, which examines how many copies of genes are missing or overabundant within the tumour cells.

Sixty samples underwent both forms of testing, which allowed researchers to explore whether combining the two tests was more powerful than each alone.

Of the samples tested by OncoPanel, 56 percent harboured genetic abnormalities that were clinically relevant - that could impact a patient's diagnosis or be targeted by drugs already in clinical use or under study in clinical trials.

(Many of these drugs cross the blood-brain barrier, the dense web of cells that can prevent medicines from exiting the bloodstream to reach the brain.) Among the findings:

• Alterations were found in the gene BRAF, one of the most commonly mutated genes in paediatric brain tumours, and one for which several targeted drugs are being tested.
• The two-pronged testing approach revealed clinically relevant abnormalities in 89 percent of medulloblastomas, which account for nearly a fifth of all brain tumours in children. Combining the two tests was found to be particularly useful for these patients.

"The importance of genomic profiling in the diagnosis and treatment of paediatric brain cancers is reflected in the World Health Organization's recent decision to classify such tumours by the genetic alterations within them, rather than by broad tumour type" says study co-senior author Susan Chi, MD, of Dana-Farber/Boston Children's. "Targeted therapies are likely to be most effective when they're matched to specific abnormalities within tumour cells. Our findings show that precision medicine for paediatric brain tumours can now be a reality."