Targetable molecular alterations in congenital glioblastoma

J Neurooncol. 2020 Jan;146(2):247-252. doi: 10.1007/s11060-019-03377-8. Epub 2019 Dec 24.


Introduction: Congenital glioblastomas (cGBMs) are uncommon tumors presenting in early infancy, variably defined as diagnosed at birth or at age less than 3 months by strict criteria, or more loosely, as occurring in very young children less than 12 months of age. Previous studies have shown that cGBMs are histologically indistinguishable from GBMs in older children or adults, but may have a more favorable clinical outcome, suggesting biological differences between congenital versus other GBMs. Due to the infrequency of cGBMs, especially when employing strict inclusion criteria, molecular features have not been sufficiently explored.

Methods: Archer FusionPlex Solid Tumor Kit, Archer VariantPlex Solid Tumor Kit, Illumina RNAseq were utilized to study cGBMs seen at our institution since 2002. A strict definition for cGBM was utilized, with only infants less than age 3 months at clinical presentation sought for this study.

Results: Of the 8 cGBM cases identified in our files, 7 had sufficient materials for molecular analyses, and 3 of 7 cases analyzed showed fusions of the ALK gene (involving MAP4, MZT2Bex2 and EML4 genes as fusion partners). One case showed ROS1 fusion. Somatic mutations in TSC22D1, BMG1 and DGCR6 were identified in 1 case. None of the cases showed alterations in IDH1/2, histone genes, or the TERT gene, alterations which can be associated with GBMs in older children or adults.

Conclusions: Our results show that cGBMs are genetically heterogeneous and biologically different from pediatric and adult GBMs. Identification of ALK and ROS1 raise the possibility of targeted therapy with FDA-approved targeted inhibitors.

Keywords: ALK; Astrocytoma; Congenital; Fetal; Glioblastoma; Infant; NTRK; Neonatal; Pediatric; ROS1.

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / congenital*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Female
  • Genetic Variation*
  • Glioblastoma / congenital*
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Prognosis
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics


  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • ROS1 protein, human