Precision Medicine Plays a Role in Pediatric Brain Tumors

Many childhood brain tumors harbor potentially targetable gene mutations, according to a prospective single-institution study of more than 200 tumor samples, researchers reported in the journal Neuro-Oncology.

“Our findings show that precision medicine for pediatric brain tumors can now be a reality,” said co-senior study author Susan Chi, MD, of the Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center.

The study represents “the largest cohort of pediatric brain tumors that have undergone genomic profiling in a CLIA-certified setting,” the authors noted.

“Although there has been a great deal of progress over the past 30 years in improving survival rates for children with cancer, advances in pediatric brain cancer haven’t been as dramatic,” noted study coauthor Pratiti Bandopadhayay, MBBS, PhD, also of Dana-Farber/Boston Children’s.

Brain tumors represent a quarter of all pediatric cancer deaths, Dr. Bandopadhayay noted.

Using OncoPanel and OncoCopy, the research team sequenced 300 cancer-causing genes to detect mutations and gene rearrangements or performed genome-wide assessments of gene copy number alterations in 203 pediatric brain tumor samples representing all histological subtypes. Sixty of the samples were analyzed using both assays. OncoPanel is a targeted next-generation exome sequencing assay that employs the Agilent SureSelect for target capture and Illumina HiSeq sequencing using formalin-fixed paraffin embedded tumor tissue.

OncoPanel analysis revealed “clinically-relevant” mutations in 56% of patients, including 44 mutations and 20 gene rearrangements. Aberrations for which targeted agents are undergoing pediatric clinical cancer trials included BRAF, IDH1, PIK3CA, PDGFRA, and KIT mutations, the authors noted; mutations for which investigational targeted agents will soon enter early-phase trials included FGFR1, NTRK 2/3/4, MYC, and MYCN. Mutations included BRAF variants; rearrangements included BRAF, MYB-QK1, MYBL1, and FGFR1 loci.

Copy number profiles varied among different histological tumor types but “the combined use of OncoPanel and OncoCopy identified subgroup-specific alterations in 89% (17/19) of medulloblastomas” studied, the authors noted.

Genomic profiling might also be useful in diagnostic classification of tumors.

“Our finding that copy number profiles broadly differ between embryonal and glial lineages holds the potential to further improve accuracy and reproducibility of diagnostics, particularly as increased numbers of tumors are profiled,” they wrote.

Combining OncoPanel and OncoCopy assay analyses “can identify critical diagnostic, prognostic, and treatment-relevant alterations and represents an effective precision medicine approach for clinical evaluation of pediatric brain tumors,” they concluded.

The prognostic and predictive values of OncoPanel and OncoCopy results have not yet been evaluated. The impact of intertumoral genomic heterogeneity on these findings needs to be studied, the authors cautioned.