Literature Review

Genomic Profiling May Improve Pediatric Brain Tumor Treatment

Next-generation sequencing of pediatric gliomas provides objective data that promote diagnostic accuracy.


 

Genomic profiling of 282 pediatric gliomas detected genetic alterations in 96% of the cases, according to research published online ahead of print September 14 in the Oncologist. Information about genetic alterations may inform prognosis and help identify effective treatments, the researchers said.

Shakti Ramkissoon, MD, PhD, Associate Medical Director at Foundation Medicine in Morrisville, North Carolina, and colleagues studied 125 low-grade gliomas and 157 high-grade gliomas taken from children at medical centers in the US. Foundation Medicine, a genomic profiling company based in Cambridge, Massachusetts, supported the study, which is the largest to date of pediatric gliomas profiled by next-generation sequencing.

The investigators sequenced 315 cancer-related genes and 28 genes commonly rearranged in cancer. Patients’ median age was 11, and 50% were male.

The most frequently altered genes differed between low- and high-grade gliomas. In low-grade gliomas, BRAF was altered in 48% of cases. In addition, FGFR1 missense (17.6%), NF1 loss of function (8.8%), and TP53 (5.6%) mutations also were detected. Among high-grade gliomas, the genes most frequently mutated were TP53 (49%), H3F3A (37.6%), ATRX (24.2%), NF1 (22.2%), and PDGFRA (21.7%).

Studies indicate that low-grade gliomas with BRAF fusions, compared with BRAF mutations, have better outcomes, Dr. Ramkissoon said. “Therefore, determining the BRAF status for all pediatric low-grade gliomas is important for clinical management,” he said.

In addition, genetic mutations may highlight potential therapeutic targets. “Although surgical resection remains the most effective treatment option for pediatric low-grade gliomas, tumors located in eloquent areas not amenable to surgical resection (eg, motor cortex) require alternative therapeutic strategies,” the researchers said. “We report a multiply recurrent NF1-mutated pilocytic astrocytoma previously treated with surgery alone that now shows a remarkable response to dual inhibitor therapy (everolimus and trametinib) following three months of treatment.”

The study demonstrates that genomic profiling can be integrated into routine clinical practice, Dr. Ramkissoon said. “Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision-making,” the researchers concluded.

—Jake Remaly

Suggested Reading

Johnson A, Severson E, Gay L, et al. Comprehensive genomic profiling of 282 pediatric low- and high-grade gliomas reveals genomic drivers, tumor mutational burden, and hypermutation signatures. Oncologist. 2017 Sep 14 [Epub ahead of print].

Weller M, Weber RG, Willscher E, et al. Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol. 2015;129(5):679-693.

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