Results from a large clinical study showed that testing pediatric brain tumors for genetic abnormalities is feasible and could play a role in guiding patients’ treatment.
The study, published in Neuro-Oncology, showed that more than half of the samples taken from pediatric brain tumors and analyzed using genomic profiling had genetic irregularities that could influence how the disease was diagnosed or treated with approved drugs or agents being evaluated in clinical trials.
“Histological diagnoses of pediatric brain tumors based on the current WHO CNS classification present diagnostic challenges, with a number of tumors that cannot be reliably distinguished,” wrote Pratiti Bandopadhayay, MBBS, PhD, of Dana-Farber Cancer Institute and Boston Children’s Hospital, and colleagues. “The classification of pediatric brain tumors based on genomic profiling provides both diagnostic and prognostic insight into many disease types. Thus, the ability to diagnose pediatric brain tumors based on genomic profiles is likely to be of great clinical utility.”
For the study, the researchers used two tests to assess single nucleotide variants and rearrangements from 203 pediatric brain tumor samples: OncoPanel, a target exome-sequencing platform that includes 300 cancer-causing genes; and OncoCopy, a clinical genome-wide array comparative genomic hybridization assay. Sixty samples underwent both forms of testing, which allowed researchers to explore whether combining the two tests was more powerful than each alone.
Using OncoPanel, the researchers found that 56% of the samples had clinically relevant alterations including 44 cancer mutations and 20 rearrangements. These alterations included BRAF mutations that directed the use of targeted BRAF inhibitors.
“Mutations were observed in a number of genes of direct relevance to pediatric brain tumor diagnosis and treatment, including BRAF, FGFR1, NTRK1, ATRX, TP53, and IDH1 in glial tumors, and CTNNB1 and PTCH1 mutations in medulloblastoma,” the researchers wrote. “We also observed driver mutations previously reported: KIT in germinoma; VHL mutations in hemangioblastomas; and the single case of primary CNS melanoma in association with neurocutaneous melanocytosis was driven by a mutation of NRAS (p.Q61K) as previously described.”
When testing was done with both OncoPanel and OncoCopy, results showed subgroup-specific alterations in 89% of medulloblastoma samples tested.
“Targeted therapeutics for specific genomic alterations in medulloblastoma are likely to have an increasing role in the treatment of children with medulloblastoma, highlighting the necessity of implementing technologies that allow the subtyping of medulloblastoma in the clinical setting,” the researchers wrote. “We believe that leveraging these findings provides a more clinically useful route to tumor classification.”