ABSTRACT
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.
Subject(s)
Brain Stem Neoplasms/genetics , Glioma/genetics , Histones/genetics , Mutation , Adolescent , Brain Stem Neoplasms/pathology , Cell Cycle Proteins/genetics , Child , Child, Preschool , DNA Topoisomerases, Type I/genetics , Exome , F-Box Proteins/genetics , F-Box-WD Repeat-Containing Protein 7 , Female , Gene Dosage , Glioma/pathology , Humans , Infant , Infant, Newborn , Male , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Young AdultABSTRACT
BACKGROUND: The meningeal hemangiopericytoma (MHPC) is a vascular tumor arising from pericytes. Most intracranial MHPCs resemble meningiomas (MNGs) in their clinical presentation and histological features and may therefore be misdiagnosed, despite important differences in prognosis. MATERIALS AND METHODS: We report 8 cases of MHPC and 5 cases of MNG collected from 2007 to 2011 from the Neuro-Surgery and Histopathology departments. All 13 samples were re reviewed by two independent pathologists and investigated by immunohistochemistry (IHC) using mesenchymal, epithelial and neuro-glial markers. Additionally, we screened all tumors for a large panel of chromosomal alterations using multiplex ligation probe amplification (MLPA). Presence of the NAB2-STAT6 fusion gene was inferred by immunohistochemical staining for STAT6. RESULTS: Compared with MNG, MHPCs showed strong VIM (100% of cases), CD99 (62%), bcl-2 (87%), and p16 (75%) staining but only focal positivity with EMA (33%) and NSE (37%). The p21 antibody was positive in 62% of MHPC and less than 1% in all MNGs. MLPA data did not distinguish HPC from MNG, with PTEN loss and ERBB2 gain found in both. By contrast, STAT6 nuclear staining was observed in 3 MHPC cases and was absent from MNG. CONCLUSIONS: MNG and MHPC comprise a spectrum of tumors that cannot be easily differentiated based on histopathology. The presence of STAT6 nuclear positivity may however be a useful diagnostic marker.
Subject(s)
Hemangiopericytoma/chemistry , Hemangiopericytoma/genetics , Meningeal Neoplasms/chemistry , Meningeal Neoplasms/genetics , Meningioma/chemistry , Meningioma/genetics , 12E7 Antigen , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD/analysis , Cell Adhesion Molecules/analysis , Cyclin-Dependent Kinase Inhibitor p16/analysis , Cyclin-Dependent Kinase Inhibitor p16/genetics , ErbB Receptors/genetics , Female , Hemangiopericytoma/pathology , Humans , Immunohistochemistry , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Multiplex Polymerase Chain Reaction , PTEN Phosphohydrolase/genetics , Proto-Oncogene Proteins c-bcl-2/analysis , Receptor, ErbB-2/genetics , STAT6 Transcription Factor/analysis , Tumor Suppressor Protein p53/genetics , Vimentin/analysisABSTRACT
BACKGROUND: Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. MATERIALS AND METHODS: We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. RESULTS: Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. CONCLUSIONS: This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.
