Genome sequencing identifies somatic BRAF duplication c.1794_1796dupTAC;p.Thr599dup in pediatric patient with low-grade ganglioglioma

Cold Spring Harb Mol Case Stud. 2018 Apr 2;4(2):a002618. doi: 10.1101/mcs.a002618. Print 2018 Apr.

Abstract

Gangliogliomas (WHO grade I) are rare tumors affecting the central nervous system and are most frequently observed in children. Next-generation sequencing of tumors is being utilized at an increasing rate in both research and clinical settings to characterize the genetic factors that drive tumorigenesis. Here, we report a rare BRAF somatic mutation (NM_004333.4:c.1794_1796dupTAC; p.Thr599dup) in the tumor genome from a pediatric patient in her late teens, who was initially diagnosed with low-grade ganglioglioma at age 13. This duplication of 3 nt introduces a second threonine residue at amino acid 599 of the BRAF protein. Based on previous studies, this variant is likely to increase kinase activity, similar to the well-characterized BRAF p.Val600Glu (V600E) pathogenic variant. In addition, although the p.T599dup somatic mutation has been documented rarely in human cancers, the variant has not been previously reported in ganglioglioma. The identification of this variant presents an opportunity to consider targeted therapy (e.g., BRAF inhibitor) for this patient.

Keywords: glioma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles*
  • Amino Acid Substitution*
  • Exome Sequencing
  • Female
  • Ganglioglioma / diagnostic imaging
  • Ganglioglioma / genetics*
  • Ganglioglioma / pathology*
  • Gene Duplication*
  • Genomics* / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Magnetic Resonance Imaging
  • Neoplasm Grading
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sequence Analysis, DNA
  • Whole Genome Sequencing

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf