Understanding Ependymoma Oncogenesis: an Update on Recent Molecular Advances and Current Perspectives

Remarkable progress has been made in the last decade in understanding the biology and oncogenesis of this relatively rare childhood brain tumor-the ependymoma. Surgery and irradiation are the mainstays of therapeutic options; chemotherapy is yet to predictably affect outcome, and its role is currently being explored in several clinical trials. While WHO scores this tumor into three grades, grading of ependymoma into grade II and grade III is controversial because of its elusive histological criteria where no cut-offs have been defined for mitoses or percentage of tumor depicting increased cellularity. Grading remains unreliable in predicting outcome in several instances. There is a compelling need to integrate the molecular biomarkers highlighted in several studies over the past decade into patient risk stratification to help in better predicting the clinical outcome and to design effective tailored therapy. Genomic and transcriptomic studies lately have defined distinct molecular subgroups within ependymoma arising at three anatomic compartments-supratentorial, posterior fossa, and spinal cord. Review of pertinent literature on several seminal studies that have established a paradigm shift in understanding the oncogenesis of ependymoma has been carried out. The outcome, impact, and clinical relevance of these studies are also discussed. The review provides an update on progress and recent advances in understanding the biology and oncogenesis of ependymoma. The establishment of robust subgroups which are demographically, clinically, and molecularly distinct will provide new avenues for further refinement of therapeutic strategies.