Journal Article

ETMR: a tumor entity in its infancy

Kool, Marcel, Lambo, Sander, Pfister, Stefan M., Korshunov, Andrey, von Hoff, Katja

2020

Overview

Embryonal tumor with Multilayered Rosettes (ETMR) is a relatively rare but typically deadly type of brain tumor that occurs mostly in infants. Since the discovery of the characteristic chromosome 19 miRNA cluster ( C19MC ) amplification a decade ago, the methods for diagnosing this entity have improved and many new insights in the molecular landscape of ETMRs have been acquired. All ETMRs, despite their highly heterogeneous histology, are characterized by specific high expression of the RNA-binding protein LIN28A, which is, therefore, often used as a diagnostic marker for these tumors. ETMRs have few recurrent genetic aberrations, mainly affecting the miRNA pathway and including amplification of C19MC (embryonal tumor with multilayered rosettes, C19MC -altered) and mutually exclusive biallelic DICER1 mutations of which the first hit is typically inherited through the germline (embryonal tumor with multilayered rosettes, DICER1- altered). Identification of downstream pathways affected by the deregulated miRNA machinery has led to several proposed potential therapeutical vulnerabilities including targeting the WNT, SHH, or mTOR pathways, MYCN or chromosomal instability. However, despite those findings, treatment outcomes have only marginally improved, since the initial description of this tumor entity. Many patients do not survive longer than a year after diagnosis and the 5-year overall survival rate is still lower than 30%. Thus, there is an urgent need to translate the new insights in ETMR biology into more effective treatments. Here, we present an overview of clinical and molecular characteristics of ETMRs and the current progress on potential targeted therapies.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Biomarkers, Tumor - genetics / Brain cancer / Brain Neoplasms - genetics / Brain Neoplasms - pathology / Brain tumors / Chromosome 19 / Gene Expression Profiling - methods / Genomic instability / Humans / Infant / Infants / Medicine / Medicine & Public Health / MicroRNAs - genetics / miRNA / Neoplasms, Germ Cell and Embryonal - genetics / Neoplasms, Germ Cell and Embryonal - pathology / Neuroectodermal Tumors, Primitive - diagnosis / Neuroectodermal Tumors, Primitive - genetics / Neuroectodermal Tumors, Primitive - pathology / Neurosciences / Pathology / Review / RNA-binding protein / TOR protein / Wnt protein