Malignant transformation of diffuse astrocytoma to glioblastoma associated with newly developed BRAF V600E mutation

A 29-year-old man presented with scintillation scotoma. MR imaging demonstrated a diffuse lesion in right parahippocampal gyrus. He underwent a biopsy, and the diagnosis was diffuse astrocytoma. Because of enlargement and new areas of gadolinium enhancement, the tumor was resected 18 months after biopsy. Histological examination revealed malignant transformation to glioblastoma with small areas of epithelioid component. He received radiation and temozolomide chemotherapy. Local recurrence was found 20 months after first resection. He underwent second resection, and the diagnosis was glioblastoma. DNA from the micro-dissected paraffin-embedded sections were analyzed for the mutation of the isocitrate dehydrogenase1 (IDH1) and IDH2 and v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) genes. No mutations of the IDH genes were detected in any tumor specimen. In contrast, missense mutation at codon 600 in the BRAF gene (BRAF V600E) was found exclusively in the malignant areas from both resected glioblastoma specimens. We screened other genetic aberrations commonly seen in glioblastoma with multiplex ligation-dependent probe analysis. Deletion of CDKN2A and CDKN2B loci was found both in diffuse astrocytoma and glioblastoma component, but no other significant alterations were found. This case suggests that the BRAF V600E mutation may be involved in the malignant transformation to glioblastoma.