Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

SummaryDespite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (367 K)Download as PowerPoint slideHighlights► There are two molecularly distinct groups of posterior fossa ependymoma ► The two subgroups are transcriptionally, genetically, and clinically divergent ► The two subgroups are distinguished by different signaling pathways ► IHC allows for routine subgroup assignment and patient prognostication