Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas.
The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of IDH-mutated gliomas and affect surgical planning. In addition, IDH1 and IDH2 mutation status may have an effect on surgical resectability of gliomas. The IDH-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation and 1p19q codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies.
Department of Neurology, Clinical Neurosciences Center;
Ricky
R
Chen
Vijay M
VM
Ravindra
Adam L
AL
Cohen
Randy L
RL
Jensen
Karen L
KL
Salzman
Andrew P
AP
Prescot
Howard
H
Colman
D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003657:Decision Making; D057890:Epigenomics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005910:Glioma / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation / Q000235:genetics; D019635:Neurosurgical Procedures / Q000379:methods*; D025521:Tumor Suppressor Proteins / Q000235:genetics
D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
1H HR-MAS = proton high-resolution magic angle spinning; 2HG = D-2-hydroxyglutarate; D-2-hydroxyglutarate spectrometry; EORTC = European Organisation for Research and Treatment of Cancer; G-CIMP = glioma CpG island methylator phenotype; GBM = glioblastoma multiforme; HR = hazard ratio; IDH = isocitrate dehydrogenase; LGG = low-grade glioma; MGMT = O6-methylguanine-DNA-methyltransferase; MRS = MR spectroscopy; OS = overall survival; PCV = procarbazine, lomustine, and vincristine; PFS = progression-free survival; RTOG = Radiation Therapy Oncology Group; astrocytoma; brain tumor; glioma; isocitrate dehydrogenase; magnetic resonance spectrometry; oligodendroglioma