Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.
Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.
Center for Neuro-Oncology, Davidoff Institute of Oncology, Rabin Medical Center, Campus Beilinson, Petach Tikva, 49100, Israel. talisi1@clalit.org.il.
Tali
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Siegal
D014408:Biomarkers, Tumor / Q000235:genetics*; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000075924:X-linked Nuclear Protein
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein; D045643:DNA Repair Enzymes
ATRX; BRAF; Chromosomal deletion; EGFR; High-grade glioma; IDH mutation; Low-grade glioma; MGMT; Molecular markers; Predictive markers; Prognostic markers