A prognostic gene expression signature in infratentorial ependymoma

Abstract

Patients with ependymoma exhibit a wide range of clinical outcomes that is currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggests that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse-transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically-identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

Molecular mechanisms and therapeutic targets in pediatric brain tumors

“…The clinical behavior of EPN is highly variable, with some patients experiencing a rapidly fatal clinical course and others harboring relatively slow-growing variants that may recur years after primary treatment (112,118,119). Especially in younger children, local tumor progression is one of the most important clinical problems, probably owing to both the anatomic location and the exclusion of young children from protocols involving adjuvant radiotherapy (112,(120)(121)(122). Ten-year overall survival is 64% in pediatric patients and ranges from 70 to 89% in adult patients (113).…”

Case-based review: ependymomas in adults

“…To date, 9 large molecular subgroups of ependymal tumors have been defined based on large-scale genomic profiling. 34,[36][37][38][39] They span the supratentorial, infratentorial (posterior fossa), and spinal cord anatomical compartments. Each anatomical compartment has 3 molecular subgroups (Fig.…”

Insights into ependymoma

“…Each anatomical compartment-supratentorial (forebrain), posterior fossa (hindbrain) or spinal-can house additional molecular subtypes of ependymoma. [3][4][5] Surgery and radiation are standard care as chemotherapy is ineffective in most patients. Indeed, up to 40% of ependymomas are incurable.…”