Molecular pathology of tumors of the central nervous system

• Published in: Annals of oncology Vol. 30; no. 8; pp. 1265 - 1278
• Main Authors: Kristensen, B.W., Priesterbach-Ackley, L.P., Petersen, J.K., Wesseling, P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2019; Oxford University Press
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - analysis; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brain - pathology; Brain Neoplasms - diagnosis; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - mortality; CNS tumor; DNA Methylation; Drug Resistance, Neoplasm - genetics; embryonal tumor; Gene Expression Regulation, Neoplastic - drug effects; glioma; Glioma - diagnosis; Glioma - drug therapy; Glioma - genetics; Glioma - mortality; Humans; Immunohistochemistry; integrated diagnosis; medulloblastoma; molecular pathology; Molecular Targeted Therapy - methods; Mutation; Neoplasms, Germ Cell and Embryonal - diagnosis; Neoplasms, Germ Cell and Embryonal - drug therapy; Neoplasms, Germ Cell and Embryonal - genetics; Neoplasms, Germ Cell and Embryonal - mortality; Prognosis; Reviews; Survival Rate; Treatment Outcome; CNS tumor; glioma; embryonal tumor; integrated diagnosis; medulloblastoma; molecular pathology
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz164

Since the update of the 4th edition of the WHO Classification of Central Nervous System (CNS) Tumors published in 2016, particular molecular characteristics are part of the definition of a subset of these neoplasms. This combined ‘histo-molecular’ approach allows for a much more precise diagnosis of especially diffuse gliomas and embryonal CNS tumors. This review provides an update of the most important diagnostic and prognostic markers for state-of-the-art diagnosis of primary CNS tumors. Defining molecular markers for diffuse gliomas are IDH1/IDH2 mutations, 1p/19q codeletion and mutations in histone H3 genes. Medulloblastomas, the most frequent embryonal CNS tumors, are divided into four molecularly defined groups according to the WHO 2016 Classification: wingless/integrated (WNT) signaling pathway activated, sonic hedgehog (SHH) signaling pathway activated and tumor protein p53 gene (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH-activated. Molecular characteristics are also important for the diagnosis of several other CNS tumors, such as RELA fusion-positive subtype of ependymoma, atypical teratoid rhabdoid tumor (AT/RT), embryonal tumor with multilayered rosettes, and solitary fibrous tumor/hemangiopericytoma. Immunohistochemistry is a helpful alternative for further molecular characterization of several of these tumors. Additionally, genome-wide methylation profiling is a very promising new tool in CNS tumor diagnostics. Much progress has thus been made by translating the most relevant molecular knowledge into a more precise clinical diagnosis of CNS tumors. Hopefully, this will enable more specific and more effective therapeutic approaches for the patients suffering from these tumors.