Genomic Alterations in Molecularly Defined Oligodendrogliomas

Carly Weber-Levine; Maureen Rakovec; Kelly Jiang; Anita Kalluri; Divyaansh Raj; Megan Parker; Joshua Materi; Sadra Sepehri; Abel Ferrés; Karisa C Schreck; Iban Aldecoa; Calixto-Hope G Lucas; Kristin J Redmond; Matthias Holdhoff; Haris I Sair; Jon D Weingart; Henry Brem; Josep González Sánchez; Xiaobu Ye; Chetan Bettegowda; Jordina Rincon-Torroella

doi:10.1227/neu.0000000000003078

Genomic Alterations in Molecularly Defined Oligodendrogliomas

Neurosurgery. 2024 Jul 15. doi: 10.1227/neu.0000000000003078. Online ahead of print.

Authors

Carly Weber-Levine¹, Maureen Rakovec², Kelly Jiang¹, Anita Kalluri¹, Divyaansh Raj¹, Megan Parker¹, Joshua Materi¹, Sadra Sepehri¹, Abel Ferrés³, Karisa C Schreck^{4

5}, Iban Aldecoa^{6

7}, Calixto-Hope G Lucas⁸, Kristin J Redmond⁹, Matthias Holdhoff^{4

5}, Haris I Sair^{10

11}, Jon D Weingart¹, Henry Brem¹, Josep González Sánchez^{3

12}, Xiaobu Ye¹, Chetan Bettegowda¹, Jordina Rincon-Torroella^{1

12

13}

Affiliations

¹ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Neurosurgery, University of Maryland Medical Center, Baltimore, Maryland, USA.
³ Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain.
⁴ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Pathology, Biomedical Diagnostic Center (CDB), Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
⁷ Neurological Tissue Bank of the Biobank Hospital Clinic Barcelona-FCRB/IDIBAPS, Barcelona, Spain.
⁸ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ The Malone Center for Engineering in Healthcare, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
¹² Laboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona, Barcelona, Spain.
¹³ Programa de Doctorat de Medicina i Recerca Translacional, Universitat de Barcelona, Barcelona, Spain.

PMID: 39007559
DOI: 10.1227/neu.0000000000003078

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. χ2 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.