Genomic Alterations in Molecularly Defined Oligodendrogliomas.

Autor:	Weber-Levine C; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Rakovec M; Department of Neurosurgery, University of Maryland Medical Center, Baltimore, Maryland, USA., Jiang K; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Kalluri A; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Raj D; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Parker M; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Materi J; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Sepehri S; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Ferrés A; Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain., Schreck KC; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Aldecoa I; Department of Pathology, Biomedical Diagnostic Center (CDB), Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.; Neurological Tissue Bank of the Biobank Hospital Clinic Barcelona-FCRB/IDIBAPS, Barcelona, Spain., Lucas CG; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Redmond KJ; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Holdhoff M; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Sair HI; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; The Malone Center for Engineering in Healthcare, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA., Weingart JD; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Brem H; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., González Sánchez J; Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain.; Laboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona, Barcelona, Spain., Ye X; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Bettegowda C; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Rincon-Torroella J; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Laboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona, Barcelona, Spain.; Programa de Doctorat de Medicina i Recerca Translacional, Universitat de Barcelona, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Neurosurgery [Neurosurgery] 2024 Jul 15. Date of Electronic Publication: 2024 Jul 15.
DOI:	10.1227/neu.0000000000003078
Abstrakt:	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. (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu