Genomic Alterations in Molecularly Defined Oligodendrogliomas.
Journal
Neurosurgery
ISSN: 1524-4040
Titre abrégé: Neurosurgery
Pays: United States
ID NLM: 7802914
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
21
12
2023
accepted:
26
04
2024
medline:
15
7
2024
pubmed:
15
7
2024
entrez:
15
7
2024
Statut:
aheadofprint
Résumé
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. 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. 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). 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.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 39007559
doi: 10.1227/neu.0000000000003078
pii: 00006123-990000000-01284
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © Congress of Neurological Surgeons 2024. All rights reserved.
Références
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.
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.
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.
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.
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.
Cahill DP, Louis DN, Cairncross JG. Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1. CNS Oncol. 2015;4(5):287-294.
Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol. 1994;145(5):1175-1190.
Eisenreich S, Abou-El-Ardat K, Szafranski K, et al. Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing. PLoS One. 2013;8(9):e76623.
Lauber C, Klink B, Seifert M. Comparative analysis of histologically classified oligodendrogliomas reveals characteristic molecular differences between subgroups. BMC Cancer. 2018;18(1):399.
Brat DJ, Verhaak RGW, et al.Cancer Genome Atlas Research Network Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372(26):2481-2498.
Labussière M, Idbaih A, Wang XW, et al. All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology. 2010;74(23):1886-1890.
Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803-820.
Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231-1251.
Rincon-Torroella J, Rakovec M, Materi J, et al. Current and future frontiers of molecularly defined oligodendrogliomas. Front Oncol. 2022;12:934426.
Chan AKY, Pang JCS, Chung NYF, et al. Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors. Mod Pathol. 2014;27(3):332-342.
Jiao Y, Killela PJ, Reitman ZJ, et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget. 2012;3(7):709-722.
Bettegowda C, Agrawal N, Jiao Y, et al. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science. 2011;333(6048):1453-1455.
Yip S, Butterfield YS, Morozova O, et al. Concurrent CIC mutations, IDH mutations and 1p/19q loss distinguish oligodendrogliomas from other cancers. J Pathol. 2012;226(1):7-16.
Sahm F, Koelsche C, Meyer J, et al. CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. Acta Neuropathol. 2012;123(6):853-860.
Nagaishi M, Suzuki A, Nobusawa S, Yokoo H, Nakazato Y. Alpha-internexin and altered CIC expression as a supportive diagnostic marker for oligodendroglial tumors with the 1p/19q co-deletion. Brain Tumor Pathol. 2014;31(4):257-264.
Synhaeve NE, van den Bent MJ, French PJ, et al. Clinical evaluation of a dedicated next generation sequencing panel for routine glioma diagnostics. Acta Neuropathol Commun. 2018;6(1):126.
Craven KE, Fischer CG, Jiang LQ, Pallavajjala A, Lin MT, Eshleman JR. Optimizing insertion and deletion detection using next-generation sequencing in the clinical laboratory. J Mol Diagn. 2022;24(12):1217-1231.
Pallavajjala A, Haley L, Stinnett V, et al. Utility of targeted next-generation sequencing assay to detect 1p/19q co-deletion in formalin-fixed paraffin-embedded glioma specimens. Hum Pathol. 2022;126:63-76.
Creed J, Gerke T, Berglund A. MatSurv: survival analysis and visualization in MATLAB. J Open Source Softw. 2020;5(46):1830.
Mark. chi2cont. 2023. https://www.mathworks.com/matlabcentral/fileexchange/45203-chi2cont.
Wong D, Lee TH, Lum A, Tao VL, Yip S. Integrated proteomic analysis of low-grade gliomas reveals contributions of 1p-19q co-deletion to oligodendroglioma. Acta Neuropathol Commun. 2022;10(1):70.
Li L, Wang Y, Li Y, Fang S, Jiang T. Role of molecular biomarkers in glioma resection: a systematic review. Chin Neurosurg J. 2020;6(1):18.
Draaisma K, Wijnenga MMJ, Weenink B, et al. PI3 kinase mutations and mutational load as poor prognostic markers in diffuse glioma patients. Acta Neuropathol Commun. 2015;3:88.
Gleize V, Alentorn A, Connen De Kérillis L, et al. CIC inactivating mutations identify aggressive subset of 1p19q codeleted gliomas. Ann Neurol. 2015;78(3):355-374.
Weissmann S, Cloos PA, Sidoli S, Jensen ON, Pollard S, Helin K. The tumor suppressor CIC directly regulates MAPK pathway genes via histone deacetylation. Cancer Res. 2018;78(15):4114-4125.
Sinkala M, Nkhoma P, Mulder N, Martin DP. Integrated molecular characterisation of the MAPK pathways in human cancers reveals pharmacologically vulnerable mutations and gene dependencies. Commun Biol. 2021;4(1):9-16.
Zhang J, Chen QM. Far upstream element binding protein 1: a commander of transcription, translation and beyond. Oncogene. 2013;32(24):2907-2916.
Dono A, Alfaro-Munoz K, Yan Y, et al. Molecular, histological, and clinical characteristics of oligodendrogliomas: a multi-institutional retrospective study. Neurosurgery. 2022;90(5):515-522.
Arcella A, Limanaqi F, Ferese R, et al. Dissecting molecular features of gliomas: genetic loci and validated biomarkers. Int J Mol Sci. 2020;21(2):685.
Rautajoki KJ, Jaatinen S, Tiihonen AM, et al. PTPRD and CNTNAP2 as markers of tumor aggressiveness in oligodendrogliomas. Sci Rep. 2022;12(1):14083.
Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.
Holdhoff M, Cairncross GJ, Kollmeyer TM, et al. Genetic landscape of extreme responders with anaplastic oligodendroglioma. Oncotarget. 2017;8(22):35523-35531.
Liu CC, Zhang LY, Wang LM, et al. [Diagnostic and prognostic roles of loss of CIC protein expression in oligodendroglial tumors]. Zhonghua Bing Li Xue Za Zhi. 2017;46(10):679-683.
Liu Z, Liu H, Liu Z, Zhang J. Oligodendroglial tumours: subventricular zone involvement and seizure history are associated with CIC mutation status. BMC Neurol. 2019;19(1):134.
Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. New Engl J Med. 2023;389(7):589-601.
Wesseling P, van den Bent M, Perry A. Oligodendroglioma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015;129(6):809-827.
Kuo LT, Kuo KT, Lee MJ, et al. Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors. Int J Cancer. 2009;124(12):2872-2879.
Chapel DB, Schulte JJ, Berg K, et al. MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma. Mod Pathol. 2020;33(2):245-254.
Sasaki S, Takeda M, Hirose T, et al. Correlation of MTAP immunohistochemistry with CDKN2A status assessed by fluorescence in situ hybridization and clinicopathological features in CNS WHO Grade 2 and 3 meningiomas: a single center cohort study. J Neuropathol Exp Neurol. 2022;81(2):117-126.
Maragkou T, Reinhard S, Jungo P, et al. Evaluation of MTAP and p16 immunohistochemical deficiency as surrogate marker for CDKN2A/B homozygous deletion in gliomas. Pathology. 2023;55(4):466-477.
Satomi K, Ohno M, Matsushita Y, et al. Utility of methylthioadenosine phosphorylase immunohistochemical deficiency as a surrogate for CDKN2A homozygous deletion in the assessment of adult-type infiltrating astrocytoma. Mod Pathol. 2021;34(4):688-700.
Gundogdu F, Babaoglu B, Soylemezoglu F. Reliability assessment of methylthioadenosine phosphorylase immunohistochemistry as a surrogate biomarker for CDKN2A homozygous deletion in adult-type IDH-mutant diffuse gliomas. J Neuropathol Exp Neurol. 2024;83(2):107-114.