GENE-16. NEXT GENERATION SEQUENCING IDENTIFIES IDH-1, ATRX, TP53 MUTATION AND MYCN AMPLIFICATION IN GLIOBLASTOMA WITH EXTENSIVE SUBARACHNOID SPREAD: A CASE REPORT

Abstract

Glioblastoma showing primarily extensive subarachnoid spreading has much worse prognosis than intracortical glioblastoma. Nevertheless, their genetic pathogenesis is still unknown due to its low incidence. Present report is a rare case of glioblastoma with primitive neuroectodermal tumor (PNET)-like feature, showing extensive subarachnoid spread, as well as the distinguishing result of its molecular analysis using next generation sequencing (NGS). A 37-year-old male presented with a new onset, severe headache. Magnetic resonance imaging test revealed a diffuse infiltrative mass in the right frontal lobe. The tumor was also spread broadly in subarachnoid space. The patient underwent craniotomy and tumorectomy. Microscopically, glioblastoma showed PNET-like feature. Tumor cells had high nuclear/cytoplasmic ratios, oval, slightly elongated or angulated hyperchromatic nuclei, markedly increased mitotic activity, and obvious apoptotic bodies. Immunohistochemical test showed partly positivity of GFAP, CD56 and synaptophysin. For comprehensive genomic profiling, we assessed NGS based on the SNUBH Brain v1.0 (Macrogen, Seoul, South Korea) panel. This panel is designed to include all genes known to be somatically altered in human brain tumor. IDH-1 (p.Arg132His) mutation and two frame shift genetic alteration including ATRX (p.Tyr2208fs) and TP53 (p.Pro301fs) were found. Additionally, MYCN (2p24.3) amplification was identified. Estimated MYCN copy number was 18. Despite the post-operative therapy including temozolomide and radiotherapy, the tumor aggressively progressed and the patient expired nine months after the first symptom onset. Although there have been several previous reports of MYCN amplification in glioblastoma with PNET-like feature, this is the first case report which finding in glioblastoma, IDH-mutant type. IDH-1 mutation and younger age are usually associated with a better prognosis in glioblastoma patients. However, our case may suggest that when MYCN amplification coexists in IDH-mutant type, the tumor behavior could be contrarily aggressive.