TY - JOUR
T1 - Genomic Alterations in Molecularly Defined Oligodendrogliomas
AU - Weber-Levine, Carly
AU - Rakovec, Maureen
AU - Jiang, Kelly
AU - Kalluri, Anita
AU - Raj, Divyaansh
AU - Parker, Megan
AU - Materi, Joshua
AU - Sepehri, Sadra
AU - Ferrés, Abel
AU - Schreck, Karisa C.
AU - Aldecoa, Iban
AU - Lucas, Calixto Hope G.
AU - Redmond, Kristin J.
AU - Holdhoff, Matthias
AU - Sair, Haris I.
AU - Weingart, Jon D.
AU - Brem, Henry
AU - González Sánchez, Josep
AU - Ye, Xiaobu
AU - Bettegowda, Chetan
AU - Rincon-Torroella, Jordina
N1 - Publisher Copyright:
© Congress of Neurological Surgeons 2024. All rights reserved.
PY - 2025/2/1
Y1 - 2025/2/1
N2 - 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.
AB - 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.
KW - 1p19q codeletion
KW - Genomic alterations
KW - Genomic variants
KW - Glioma
KW - Next-generation sequencing
KW - Oligodendrogliomas
UR - https://www.scopus.com/pages/publications/85205874608
UR - https://www.scopus.com/pages/publications/85205874608#tab=citedBy
U2 - 10.1227/neu.0000000000003078
DO - 10.1227/neu.0000000000003078
M3 - Article
C2 - 39007559
AN - SCOPUS:85205874608
SN - 0148-396X
VL - 96
SP - 328
EP - 337
JO - Neurosurgery
JF - Neurosurgery
IS - 2
ER -