Molecular pathology of tumors of the central nervous system

Abstract

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.

Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

“…Many tumors of the brain stem have characteristic alterations (Dunham, 2015;Kristensen et al, 2019). Perhaps the most successful use for CSF cfDNA has been in the characterization of brain stem tumors, which are inherently difficult and dangerous to biopsy.…”

m6A modification in RNA: biogenesis, functions and roles in gliomas

“…Therefore, most patients receive radiotherapy and temozolomide (TMZ) combined with chemotherapy after surgery. Although the treatment intensity is very high, the outcomes are still not satisfactory [2][3][4][5]. Therefore, there is an urgent need for new treatment strategies or regimens.…”

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

“…Since the emerge of molecular biology in the 1930s, the discipline has undergone significant changes, which can be largely attributed to the description of DNA as a double-helical structure in 1953, the accomplishment of the Human Genome Project in 2003, and the rapid development of advanced diagnostic technologies. Over the years, cancer diagnostics evolved from gross and microscopic analysis toward an integrated, morphology, and molecular-based approach, leading to improved understanding of carcinogenesis and disease progression [1]. We now understand that cancer is not a monolithic disease and that a tumor is not a homogeneous mass [2]; fighting cancer not only demands an appreciation of inter-patient variability, but also requires us to outwit the intra-tumoral spatial and temporal heterogeneity.…”

“…As for CNS tumors, based on the improvement of diagnostic technologies, in May 2016, the World Health Organization (WHO) published a revised classification as an update of the 2007 edition [1,6]. For the first time, the WHO uses molecular parameters in addition to histology, which has resulted in the dismissal of a number of entities that are no longer thought to have diagnostic and/or biological value and the appointment of newly recognized neoplasms that should facilitate the development of more effective targeted therapies [6].…”