Molecular genetics and therapeutic targets of pediatric low-grade gliomas

Brain Tumor Pathol. 2019 Apr;36(2):74-83. doi: 10.1007/s10014-019-00340-3. Epub 2019 Mar 30.

Abstract

Pediatric low-grade gliomas (PLGGs) have relatively favorable prognosis and some resectable PLGGs, such as cerebellar pilocytic astrocytoma, can be cured by surgery alone. However, many PLGG cases are unresectable and some of them undergo tumor progression. Therefore, a multidisciplinary approach is necessary to treat PLGG patients. Recent genomic analysis revealed a broad genomic landscape underlying PLGG. Notably, the majority of PLGGs present MAPK pathway-associated genomic alterations and MAPK signaling-dependent tumor progression. Following preclinical evidence, many clinical trials based on molecular target therapy have been conducted on PLGG patients, some of whom exhibited durable response to target therapy. Here, we provide an overview of PLGG genetics and the evidence supporting the application of molecular target therapy in these patients.

Keywords: Genetic alteration; Molecular target therapy; Pediatric low-grade glioma.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Astrocytoma / genetics
  • Astrocytoma / pathology
  • Astrocytoma / therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Child
  • Child, Preschool
  • Glioma / genetics*
  • Glioma / pathology*
  • Glioma / therapy
  • Humans
  • Infant
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation / genetics
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Proto-Oncogene Proteins B-raf

Substances

  • BRAF-KIAA1549 fusion protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinases