Journal Article

BRAF V600E Mutations Are Common in Pleomorphic Xanthoastrocytoma: Diagnostic and Therapeutic Implications

Iafrate, A. John, Ligon, Keith L., Lam, Quynh, Borger, Darrell R., Ligon, Azra H., Louis, David N., Vernovsky, Kathy, Vena, Natalie, Santagata, Sandro, Dias-Santagata, Dora, Batchelor, Tracy T., Lennerz, Jochen K.

2011

Overview

Pleomorphic xanthoastrocytoma (PXA) is low-grade glial neoplasm principally affecting children and young adults. Approximately 40% of PXA are reported to recur within 10 years of primary resection. Upon recurrence, patients receive radiation therapy and conventional chemotherapeutics designed for high-grade gliomas. Genetic changes that can be targeted by selective therapeutics have not been extensively evaluated in PXA and ancillary diagnostic tests to help discriminate PXA from other pleomorphic and often more aggressive astrocytic malignancies are limited. In this study, we apply the SNaPshot multiplexed targeted sequencing platform in the analysis of brain tumors to interrogate 60 genetic loci that are frequently mutated in 15 cancer genes. In our analysis we detect BRAF V600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA. Phospho-ERK was detected in all tumors independent of the BRAF mutation status. BRAF duplication was not detected in any of the PXA cases. BRAF V600E mutations were identified in only 2 of 71 (2.8%) glioblastoma (GBM) analyzed, including 1 of 9 (11.1%) giant cell GBM (gcGBM). The finding that BRAF V600E mutations are common in the majority of PXA has important therapeutic implications and may help in differentiating less aggressive PXAs from lethal gcGBMs and GBMs.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Adults / Analysis / Astrocytes / Astrocytoma - diagnosis / Astrocytoma - genetics / Astrocytoma - pathology / Astrocytoma - therapy / Base Sequence / Brain / Brain cancer / Brain tumors / Cancer / Cancer therapies / Care and treatment / Cell growth / Central nervous system diseases / Chemotherapy / Child / Children / Children & youth / Diagnosis / Diagnostic systems / DNA Mutational Analysis / Extracellular signal-regulated kinase / Extracellular Signal-Regulated MAP Kinases - metabolism / Female / Gene mutation / Gene sequencing / Genetic aspects / Genotype / Glioblastoma / Glioma - diagnosis / Glioma - genetics / Glioma - pathology / Glioma - therapy / Gliomas / Health aspects / Hematology / Humans / Immunohistochemistry / In Situ Hybridization, Fluorescence / Male / Medical diagnosis / Medical prognosis / Medical research / Medical schools / Medicine / Melanoma / Metastasis / Middle Aged / Molecular Sequence Data / Mutation / Mutation - genetics / Oncology / Pathology / Phosphorylation / Polymorphism, Single Nucleotide - genetics / Proto-Oncogene Proteins B-raf - genetics / Proto-Oncogene Proteins B-raf - metabolism / Radiation / Radiation therapy / Radiotherapy / Tumors / Womens health / Young Adult / Young adults