Molecular Analysis of Pediatric Oligodendrogliomas Highlights Genetic Differences with Adult Counterparts and Other Pediatric Gliomas

Brain Pathol. 2016 Mar;26(2):206-14. doi: 10.1111/bpa.12291. Epub 2015 Aug 14.

Abstract

Oligodendroglioma represents a distinctive neoplasm in adults but similar neoplasms occur rarely in children. We studied 20 cases of pediatric oligodendroglioma by SNP array (median age 9 years, range 1-19; 15 grade II and 5 grade III). Cytogenetic abnormalities were present in 8 (53%) grade II and all five anaplastic oligodendrogliomas. Most changes were in the form of deletion and copy neutral loss of heterozygosity (LOH). The most common abnormality was 1p deletion (n = 5). Whole arm 1p19q co-deletion was present in three cases from adolescent patients and 9p loss in 3, including one low-grade oligodendroglioma with CDKN2A homozygous deletion. Common losses were largely limited to the anaplastic subset (n = 5) and included 3q29 (n = 3), 11p (n = 3), 17q (n = 3), 4q (n = 2), 6p (n = 2), 13q (n = 2), 14q (n = 2), 17p (n = 2) and whole Ch 18 loss (n = 2). Gains were non-recurrent except for whole Ch 7 (n = 2) and gain on 12q (n = 2) including the MDM2 locus. Possible germ line LOH (or uniparental disomy) was present in seven cases (35%), with one focal abnormality (22q13.1-13.2) in two. BRAF-KIAA1549 fusions and BRAF p.V600E mutations were absent (n = 13 and 8). In summary, cytogenetic alterations in pediatric oligodendrogliomas are characterized mostly by genomic losses, particularly in anaplastic tumors.

Keywords: BRAF; FISH; SNP array; cytogenetics; oligodendroglioma; pediatric glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Infant
  • Loss of Heterozygosity
  • Male
  • Neoplasm Grading
  • Oligodendroglioma / genetics*
  • Oligodendroglioma / metabolism*
  • Oligodendroglioma / pathology
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Sequence Deletion
  • Young Adult

Substances

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