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Genomic Alterations in Molecularly Defined Oligodendrogliomas.

Carly Weber-Levine1, Maureen Rakovec2, Kelly Jiang1

  • 1Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore , Maryland , USA.

Neurosurgery
|July 15, 2024
PubMed
Summary

Genomic alterations in oligodendrogliomas, including CIC, FUBP1, and TERTp, were analyzed using clinical next-generation sequencing. CIC alterations may impact progression-free survival in the early stages of this brain tumor.

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Area of Science:

  • Neuro-oncology
  • Genomics
  • Cancer research

Background:

  • Oligodendrogliomas are defined by IDH1/2 mutation and 1p/19q codeletion.
  • Previous studies identified frequent alterations in CIC, FUBP1, and TERTp, but clinical relevance remains unclear.
  • Existing research often uses non-standardized panels, limiting clinical applicability.

Purpose of the Study:

  • To investigate genomic alterations in molecularly defined oligodendrogliomas using clinically standardized next-generation sequencing (NGS) panels.
  • To explore the clinical relevance of frequently altered genes, such as CIC, FUBP1, and TERTp.
  • To assess the association of these genomic variants with patient outcomes.

Main Methods:

  • Retrospective analysis of adult patients with IDH-mutant, 1p/19q-codeleted oligodendrogliomas (2005-2021).
  • Analysis of genetic data from formalin-fixed, paraffin-embedded specimens using the NGS Solid Tumor Panel.
  • Comparison of progression-free survival (PFS) and overall survival by variant status using Kaplan-Meier plots and log-rank tests.

Main Results:

  • Ninety-five patients with available NGS reports were identified among 277 molecularly defined oligodendrogliomas.
  • CIC (n=60), FUBP1 (n=23), and TERTp (n=22) were the most frequently altered genes.
  • Most gene alterations did not significantly impact PFS or overall survival, but CIC alterations were associated with reduced PFS at earlier time points (PFS <100 months, P=.038).

Conclusions:

  • Confirms high frequency of CIC, FUBP1, and TERTp alterations in oligodendrogliomas.
  • Suggests a potential link between CIC alterations and reduced PFS in early disease stages.
  • Highlights the potential of understanding genomic variants for prognosis and therapeutic guidance as NGS becomes standard clinical practice.