HGG-07. THREE SUCCESSIVE BIOPSIES DEMONSTRATE CLONAL EVOLUTION IN A MULTIPLY-RECURRENT PEDIATRIC GLIOFIBROMA

Abstract

Gliofbroma is a rare central nervous system (CNS) tumor with yet-undescribed molecular characteristics. We describe a 20-month-old boy presenting with a large infltrative gliofbroma arising in the left midbrain. The tumor was partially resected and the pathology was consistent with gliofbroma with low proliferation. Magnetic resonance spectroscopy of the remaining mass was consistent with a high-grade tumor. Molecular fnd-ings were signifcant for a BRAFV600E mutation and homozygous deletion of CDKN2A. The patient was treated with targeted therapy using a combination of the BRAFV600E inhibitor vemurafenib and the MEK inhibitor, trametinib, with rapid clinical response. Tumor shrinkage was sustained for at least 12 months. Routine MRI at 15 months revealed marked tumor regrowth with pathology from subsequent resection demonstrating areas of low-grade morphology as well as areas with high-grade features. Molecular fndings on the initial recurrence were notable for new PDGFRA (Asp842Tyr) and PTPN11 (Ala72Val) mutations in addition to the original genetic alterations. The patient received radiation therapy, but became symptomatic shortly prior to completion. MRI demonstrated new infltrative tumor anterior to the lateral ventricle, outside the radiation feld and extensive subependymal infltration. Resection of the new mass revealed two new mutations in TP53 (Arg196Gln) and PIK3CA (His1047Arg), in addition to the four previous alterations. To our knowledge, this is the first report on gliofbroma with extensive molecular characterization and the first reported high-grade glioma with molecular data from three successive biopsies. The observed serial acquisition of new mutations on subsequent recurrent specimens is consistent with clonal evolution of disease. The availability of three sets of molecular results on repeat biopsies is unique even to the broader diagnosis of high-grade glioma and sheds light on the biology of recurrence.