Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 1;96(2):328-337.
doi: 10.1227/neu.0000000000003078. Epub 2024 Jul 15.

Genomic Alterations in Molecularly Defined Oligodendrogliomas

Carly Weber-Levine  1 , Maureen Rakovec  2 , Kelly Jiang  1 , Anita Kalluri  1 , Divyaansh Raj  1 , Megan Parker  1 , Joshua Materi  1 , Sadra Sepehri  1 , Abel Ferrés  3 , Karisa C Schreck  4   5 , Iban Aldecoa  6   7 , Calixto-Hope G Lucas  8 , Kristin J Redmond  9 , Matthias Holdhoff  4   5 , Haris I Sair  10   11 , Jon D Weingart  1 , Henry Brem  1 , Josep González Sánchez  3   12 , Xiaobu Ye  1 , Chetan Bettegowda  1 , Jordina Rincon-Torroella  1   12   13
Affiliations

Genomic Alterations in Molecularly Defined Oligodendrogliomas

Carly Weber-Levine et al. Neurosurgery. .

Abstract

Background and objectives: Oligodendrogliomas are defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Although previous studies identified CIC , FUBP1 , and TERTp as frequently altered in oligodendrogliomas, the clinical relevance of these molecular signatures is unclear. Moreover, previous studies predominantly used research panels that are not readily available to providers and patients. Accordingly, we explore genomic alterations in molecularly defined oligodendrogliomas using clinically standardized next-generation sequencing (NGS) panels.

Methods: A retrospective single-center study evaluated adults with pathologically confirmed IDH -mutant, 1p/19q-codeleted oligodendrogliomas diagnosed between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tests more than 400 cancer-related genes. Kaplan-Meier plots and log-rank tests compared progression-free survival (PFS) and overall survival by variant status. χ 2 tests, t -tests, and Wilcoxon rank-sum tests were used to compare clinical characteristics between genomic variant status in the 10 most frequently altered genes.

Results: Two hundred and seventy-seven patients with molecularly defined oligodendrogliomas were identified, of which 95 patients had available NGS reports. Ten genes had 9 or more patients with a genomic alteration, with CIC , FUBP1 , and TERTp being the most frequently altered genes (n = 60, 23, and 22, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or overall survival. At earlier time points (PFS <100 months), CIC alterations conferred a reduction in PFS in patients ( P = .038).

Conclusion: Our study confirms the elevated frequency of CIC , FUBP1 , and TERTp alterations in molecularly defined oligodendrogliomas and suggests a potential relationship of CIC alteration to PFS at earlier time points. Understanding these genomic variants may inform prognosis or therapeutic recommendations as NGS becomes routine.

PubMed Disclaimer

References

    1. Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro Oncol. 2022;24(Suppl 5):V1-V95.
    1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372(26):2499-2508.
    1. Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014-2018. Neuro Oncol. 2021;23(12 Suppl 2):III1-III105.
    1. Kros JM, Gorlia T, Kouwenhoven MC, et al. Panel review of anaplastic oligodendroglioma from European Organization for Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome. J Neuropathol Exp Neurol. 2007;66(6):545-551.
    1. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97-109.