PTPS-01MOLECULAR PROFILING ANALYSIS OF SELECT PEDIATRIC NEUROEPITHELIAL TUMORS OF THE CENTRAL NERVOUS SYSTEM

BACKGROUND: Pediatric neuroepithelial tumors of the central nervous system (CNS) comprise a vast group of cancers where optimal treatments may be limited or non-existent given the rarity of these tumors in the pediatric population. As molecular oncology continues identifying novel treatments in adult cancers, a need exists to do the same in the pediatric population. The goal of this study is to retrospectively analyze pediatric tumors profiled at our facility to identify novel chemotherapeutic or targeted options in these diseases. METHODS: A retrospective evaluation of 44 neuroepithelial CNS tumors (e.g. astrocytic tumors, ependymal tumors, tumors with neuroblastic/glioblastic elements) tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) was performed. Testing consisted of gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (CISH/FISH). RESULTS: Patients were between the ages of 1 and 14 (mean = 7.4 years), with medulloblastoma (n = 10), glioblastoma multiforme (n = 7), and ependymoma (n = 6) being the most common histologies. In a comparison of three major subtypes, astrocytic tumors had the most gene aberrations (i.e. gene amplification or mutation) with abnormalities detected in APC, BRCA2, BRAF, EGFR, ERBB4, KDR, MGMT, and TP53. By contrast, few gene aberrations were found in ependymal tumors and neuroblastic/glioblastic tumors. Interestingly, an ALK abnormality was detected in one ependymoma. Protein evaluation by IHC yielded the most potential targets in all groups. CONCLUSION: Multiplatform tumor profiling identified several targets in molecular profiles of neuroepithelial tumors of the CNS. Astrocytic tumors, comprising anaplastic astrocytoma and glioblastoma multiforme, have the greatest number of potential targets. Ependymoma could potentially be targeted with ALK-targeted therapy capable of crossing the blood-brain barrier. Given the lack of mutations detected, a multiplatform approach may be advisable to identify the best targets in this patient population. Further studies are needed for this underserved patient population.