Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia

PLoS One. 2020 Jan 29;15(1):e0228356. doi: 10.1371/journal.pone.0228356. eCollection 2020.

Abstract

Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1-3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). Interestingly, we identified a GOPC-ROS1 fusion in an 8-year-old patient whose tumor lacked BRAF alterations and histologically classified as low grade glioma. The patient underwent gross total resection (GTR). The patient is currently disease free. To our knowledge this is the first report of GOPC-ROS1 fusion in PLGG. Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics*
  • Brain Neoplasms / surgery
  • Child
  • Child, Preschool
  • Clinical Decision-Making
  • Female
  • Gene Fusion*
  • Genomics / methods*
  • Glioma / genetics*
  • Glioma / surgery
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Male
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Retrospective Studies
  • Saudi Arabia
  • Treatment Outcome

Grants and funding

This Study was funded by KFMC-IRF 17-65 (MA) and Sanad Cancer research foundation RGP 2017-1 (MA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.