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International Journal of Epidemiology Mar 2021Central nervous system (CNS) tumours comprise 20% of childhood cancers worldwide. Whether childhood CNS tumour incidence has increased over time across geographic...
BACKGROUND
Central nervous system (CNS) tumours comprise 20% of childhood cancers worldwide. Whether childhood CNS tumour incidence has increased over time across geographic regions remains to be explored.
METHODS
We identified CNS cancers in the Cancer in Five Continents (CI5) data and estimated age standardized incidence rates (ASRs; cases/million children) and 95% confidence intervals (95% CI), male-to-female incidence rate ratios (IRR; 95% CI) and average annual percent change in incidence (AAPC; 95% CI) by geographic region for children aged 0-19 years where data were available using Poisson regression and generalized estimating equations (GEE). Cancers included: astrocytic tumours, medulloblastoma, ependymal, oligodendroglial and mixed glioma, glioma of uncertain origin, and other embryonal tumours. Geographic regions were defined using the United Nations geoscheme.
RESULTS
There were 56 468 CNS cancers included in the study. ASRs were highest for astrocytic tumours globally in 2012 (ASR: 5.83; 95% CI: 5.68-5.99). Globally, all cancers exhibited a male excess in incidence. Regionally, only medulloblastoma had a consistently elevated male-to-female IRR at 1.4-2.2. Globally, incidence decreased for astrocytic tumours in GEE models (AAPC: -1.66; 95% CI: -3.04 to -0.26) and increased for medulloblastoma (AAPC 0.66; 95% CI: 0.19-1.14), ependymal tumours (AAPC: 1.49; 95% CI: 1.49; 95%: 0.69-2.30), glioma of uncertain origin (AAPC: 4.76; 95% CI: 1.17-1.14) and other embryonal tumours (AAPC: 3.58; 95% CI: 2.03-5.15). Regional variation in incidence trends was observed. Countries moving from lower to higher Human Development Index (HDI) over time did not appear to drive observed incidence trends.
CONCLUSIONS
Epidemiologic and molecular studies on underlying mechanisms for changes in the global incidence of CNS tumours are necessary.
Topics: Adolescent; Adult; Central Nervous System Neoplasms; Child; Child, Preschool; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Young Adult
PubMed: 33221912
DOI: 10.1093/ije/dyaa176 -
Neurology India 2020Low grade gliomas (LGG) are most often noted with the unpredictable overall survival and progression to higher grades. Objective: In the present study, we analyze the...
BACKGROUND
Low grade gliomas (LGG) are most often noted with the unpredictable overall survival and progression to higher grades. Objective: In the present study, we analyze the clinicopathological features influencing the prognostic outcomes and compared the features with criteria developed by EORTC.
MATERIALS AND METHODS
We observed the 130 LGG clinical cases in single institute and maintained the follow-up for more than 5 years. In addition, the molecular details were confirmed with markers as IDH, 1p/19q codeletion, p53 and ATRX mutations.
RESULTS
The mean age of patients as 37.67 years and male population contributing to 70%. We observed biased incidence among the male population with dominating occurrence at frontal and parietal lobes in the brain. 40.8% patients had oligodendroglioma, 33.8% astrocytoma, 19.2% oligoastrocytoma and 2.3% gemistocytic astrocytoma pathology. Patients who were subjected to chemotherapy and radiotherapy were noted with average survival of 29 months. Oligodendroglial tumors were found with progression free survival (PFS) of 25 months, oligoastrocytoma cases with 32 months, diffuse astrocytoma cases with 23 months while the gemistocytic astrocytoma cases had 22 months. The PFS for LGG cases was 4.7 years while the overall survival was 4.9 years. Mean survival of patients with KPS score <70 and >70 was 1.5 & 4.9 years respectively. 64 patients were observed with the tumor size >5 cm. In total, 72.3% of the patients were underwent GTR, 23.3% STR and 3.8% underwent biopsy.
CONCLUSION
Taken together, the clinical symptoms, expression of molecular markers and the prognosis details provided by our results can help for better management of LGG cases. We further propose to use following five factors to accurately describe the prognosis and tumor recurrence: 1) Age >50 years, 2) tumor size >5 cm, 3) MIB index >5%, 4) KPS score < 70 and 5) gemistocytic pathology.
Topics: Adult; Astrocytoma; Brain Neoplasms; Glioma; Humans; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local; Oligodendroglioma; Prognosis; Risk Assessment
PubMed: 32859817
DOI: 10.4103/0028-3886.293441 -
Acta Neuropathologica Communications Aug 2020The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor...
The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor (LGNET) subtypes including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor (DNT), rosette-forming glioneuronal tumor (RGNT), and extraventricular neurocytoma (EVN). These activating FGFR1 alterations in LGNET can include tandem duplication of the exons encoding the intracellular tyrosine kinase domain, in-frame gene fusions most often with TACC1 as the partner, or hotspot missense mutations within the tyrosine kinase domain (either at p.N546 or p.K656). However, the specificity of these different FGFR1 events for the various LGNET subtypes and accompanying genetic alterations are not well defined. Here we performed comprehensive genomic and epigenomic characterization on a diverse cohort of 30 LGNET with FGFR1 alterations. We identified that RGNT harbors a distinct epigenetic signature compared to other LGNET with FGFR1 alterations, and is uniquely characterized by FGFR1 kinase domain hotspot missense mutations in combination with either PIK3CA or PIK3R1 mutation, often with accompanying NF1 or PTPN11 mutation. In contrast, EVN harbors its own distinct epigenetic signature and is characterized by FGFR1-TACC1 fusion as the solitary pathogenic alteration. Additionally, DNT and pilocytic astrocytoma are characterized by either kinase domain tandem duplication or hotspot missense mutations, occasionally with accompanying NF1 or PTPN11 mutation, but lacking the accompanying PIK3CA or PIK3R1 mutation that characterizes RGNT. The glial component of LGNET with FGFR1 alterations typically has a predominantly oligodendroglial morphology, and many of the pilocytic astrocytomas with FGFR1 alterations lack the biphasic pattern, piloid processes, and Rosenthal fibers that characterize pilocytic astrocytomas with BRAF mutation or fusion. Together, this analysis improves the classification and histopathologic stratification of LGNET with FGFR1 alterations.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Female; Humans; Male; Middle Aged; Mutation; Neoplasms, Neuroepithelial; Receptor, Fibroblast Growth Factor, Type 1; Spinal Cord Neoplasms; Young Adult
PubMed: 32859279
DOI: 10.1186/s40478-020-01027-z -
Asian Pacific Journal of Cancer... Aug 2020Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of...
BACKGROUND
Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas.
METHODS
In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records.
RESULTS
Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival.
CONCLUSIONS
IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia.
.Topics: Adult; Asian People; Biomarkers, Tumor; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Glioma; Humans; Indonesia; Isocitrate Dehydrogenase; Male; Mutation; Prognosis; Promoter Regions, Genetic; Prospective Studies; Retrospective Studies; Survival Rate; Tumor Suppressor Proteins
PubMed: 32856857
DOI: 10.31557/APJCP.2020.21.8.2287 -
Epidemiology of brain tumors in the United Arab Emirates: a National Registry Cross-sectional Study.BMC Neurology Aug 2020Cancer is the third leading cause of death in the United Arab Emirates (UAE); brain cancer ranks 10th among the cancers, with 2.9% of the primary cancers originating...
BACKGROUND
Cancer is the third leading cause of death in the United Arab Emirates (UAE); brain cancer ranks 10th among the cancers, with 2.9% of the primary cancers originating from the nervous system. The epidemiology of brain cancers has not been explored. The unique population dynamics of UAE make it a fertile ground for analyzing the epidemiology of brain cancer. In this study, we aim to look at the frequency patterns and distribution of malignant primary brain tumors in the UAE.
METHODS
A cross sectional study was carried out using data obtained from the Tawam Hospital Cancer Registry for the years 1984-2017. The sample size included 756 diagnosed cases of malignant primary brain tumors in the UAE. Using SPSS and Excel software, frequencies, mean ages, histological type frequencies, average annual crude incidence rates and average annual age adjusted incidence rates were analyzed.
RESULTS
The expatriate population had higher percentage of brain tumors (72%) than the locals. The mean age at diagnosis was 33.48 years (± 21.14 years) with a male to female ratio of 1.69. Diffuse astrocytic and oligodendroglial tumors were the most commonly diagnosed tumors overall. Older adults had more cases of lymphoma while embryonal and ependymal tumors were most commonly seen in younger age groups. The overall average annual crude incidence rate for 2013-2016 for all primary brain tumors was 0.56 per 100,000 population.
CONCLUSION
This is the first cancer registry study in the UAE that describes histological types of primary brain tumors based on the WHO 2016 classification of brain tumors and highlights their incidence rates. Through this study, several patterns of incidence trends for brain tumors in the UAE, according to histological types, sex and age groups have been recognized. Comparative studies would help identify the influence of potential changes in lifestyle, environmental or occupational risk factors on primary brain tumors.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Registries; United Arab Emirates; Young Adult
PubMed: 32795357
DOI: 10.1186/s12883-020-01869-z -
Cancer Science Oct 2020Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations,...
Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma-tailored 48-gene next-generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma-tailored 48-gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH-wildtype glioblastomas. Within these IDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp-wildtype glioblastomas (43%) than in TERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma-tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH- and TERTp-wildtype glioblastomas with frequent PDGFRA alterations.
Topics: Adult; Aged; Aged, 80 and over; Female; Glioblastoma; High-Throughput Nucleotide Sequencing; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Neoplasm Proteins; Promoter Regions, Genetic; Receptor, Platelet-Derived Growth Factor alpha; Telomerase
PubMed: 32748499
DOI: 10.1111/cas.14597 -
Acta Neuropathologica Communications Jul 2020Multiple system atrophy (MSA) is pathologically characterized by the presence of fibrillar α-synuclein-immunoreactive inclusions in oligodendrocytes. Although the...
Multiple system atrophy (MSA) is pathologically characterized by the presence of fibrillar α-synuclein-immunoreactive inclusions in oligodendrocytes. Although the myelinating process of oligodendrocytes can be observed in adult human brains, little is known regarding the presence of α-synuclein pathology in immature oligodendrocytes and how their maturation and myelination are affected in MSA brains. Recently, breast carcinoma amplified sequence 1 (BCAS1) has been found to be specifically expressed in immature oligodendrocytes undergoing maturation and myelination. Here, we analyzed the altered dynamics of oligodendroglial maturation in both MSA brains and primary oligodendroglial cell cultures which were incubated with α-synuclein pre-formed fibrils. The numbers of BCAS1-expressing oligodendrocytes that displayed a matured morphology negatively correlated with the density of pathological inclusions in MSA brains but not with that in Parkinson's disease and diffuse Lewy body disease. In addition, a portion of the BCAS1-expressing oligodendrocyte population showed cytoplasmic inclusions, which were labeled with antibodies against phosphorylated α-synuclein and cleaved caspase-9. Further in vitro examination indicated that the α-synuclein pre-formed fibrils induced cytoplasmic inclusions in the majority of BCAS1-expressing oligodendrocytes. In contrast, the majority of BCAS1-non-expressing mature oligodendrocytes did not develop inclusions on day 4 after maturation induction. Furthermore, exposure of α-synuclein pre-formed fibrils in the BCAS1-positive phase caused a reduction in oligodendroglial cell viability. Our results indicated that oligodendroglial maturation and myelination are impaired in the BCAS1-positive phase of MSA brains, which may lead to the insufficient replacement of defective oligodendrocytes. In vitro, the high susceptibility of BCAS1-expressing primary oligodendrocytes to the extracellular α-synuclein pre-formed fibrils suggests the involvement of insufficient oligodendroglial maturation in MSA disease progression and support the hypothesis that the BCAS1-positive oligodendrocyte lineage cells are prone to take up aggregated α-synuclein in vivo.
Topics: Animals; Cell Differentiation; Humans; Multiple System Atrophy; Neoplasm Proteins; Nerve Tissue Proteins; Oligodendrocyte Precursor Cells; Oligodendroglia; Rats; Rats, Sprague-Dawley; alpha-Synuclein
PubMed: 32727582
DOI: 10.1186/s40478-020-00997-4 -
Acta Neuropathologica Communications Jun 2020Diffuse leptomeningeal glioneuronal tumor (DLGNT) was introduced, for the first time, as a provisional entity in the 2016 WHO classification of central nervous system...
Diffuse leptomeningeal glioneuronal tumor (DLGNT) was introduced, for the first time, as a provisional entity in the 2016 WHO classification of central nervous system tumors. DLGNT mainly occur in children and characterized by a widespread leptomeningeal growth occasionally associated with intraspinal tumor nodules, an oligodendroglial-like cytology, glioneuronal differentiation and MAP-Kinase activation associated with either solitary 1p deletion or 1p/19q codeletion in the absence of IDH mutation.We report here two unexpected DLGNTs adult cases, characterized by a unique supratentorial circumscribed intraparenchymal tumor without leptomeningeal involvement in spite of long follow-up. In both cases, the diagnosis of DLGNT was made after DNA-methylation profiling which demonstrated that one case belonged to the DLGNT class whereas the other remained not classifiable but showed on CNV the characteristic genetic findings recorded in DLGNT. Both cases harbored 1p/19q codeletion associated with KIAA1549:BRAF fusion in one case and with BRAF V600E and PIK3CA E545A mutations, in the other.Our study enlarges the clinical and molecular spectrum of DLGNTs, and points out that the terminology of DLGNTs is not fully appropriate since some cases could have neither diffuse growth nor leptomeningeal dissemination. This suggests that DLGNTs encompass a wide spectrum of tumors that has yet to be fully clarified.
Topics: Adult; Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Meningeal Neoplasms; Mutation; Oligodendroglioma; Proto-Oncogene Proteins B-raf
PubMed: 32605662
DOI: 10.1186/s40478-020-00978-7 -
Scientific Reports May 2020Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 are frequently found in diffuse and anaplastic astrocytic and oligodendroglial tumours as well as in secondary...
Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 are frequently found in diffuse and anaplastic astrocytic and oligodendroglial tumours as well as in secondary glioblastomas. As IDH is a very important prognostic, diagnostic and therapeutic biomarker for glioma, it is of paramount importance to determine its mutational status. The haematoxylin and eosin (H&E) staining is a valuable tool in precision oncology as it guides histopathology-based diagnosis and proceeding patient's treatment. However, H&E staining alone does not determine the IDH mutational status of a tumour. Deep learning methods applied to MRI data have been demonstrated to be a useful tool in IDH status prediction, however the effectiveness of deep learning on H&E slides in the clinical setting has not been investigated so far. Furthermore, the performance of deep learning methods in medical imaging has been practically limited by small sample sizes currently available. Here we propose a data augmentation method based on the Generative Adversarial Networks (GAN) deep learning methodology, to improve the prediction performance of IDH mutational status using H&E slides. The H&E slides were acquired from 266 grade II-IV glioma patients from a mixture of public and private databases, including 130 IDH-wildtype and 136 IDH-mutant patients. A baseline deep learning model without data augmentation achieved an accuracy of 0.794 (AUC = 0.920). With GAN-based data augmentation, the accuracy of the IDH mutational status prediction was improved to 0.853 (AUC = 0.927) when the 3,000 GAN generated training samples were added to the original training set (24,000 samples). By integrating also patients' age into the model, the accuracy improved further to 0.882 (AUC = 0.931). Our findings show that deep learning methodology, enhanced by GAN data augmentation, can support physicians in gliomas' IDH status prediction.
Topics: Adult; Aged; Deep Learning; Female; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Prognosis
PubMed: 32382048
DOI: 10.1038/s41598-020-64588-y -
PloS One 2020Despite many years of research efforts and clinical trials the prognosis of patients diagnosed with glioblastoma remains very poor. The oligodendrocyte transcription...
Despite many years of research efforts and clinical trials the prognosis of patients diagnosed with glioblastoma remains very poor. The oligodendrocyte transcription factor 2 (Olig2) was identified as a marker for glioma stem cells, which are believed to be responsible for glioma recurrence and therapy resistance. In this retrospective analysis we assessed the prognostic value of oligodendroglial and glioma stem cell markers in 113 IDH-wildtype glioblastomas. Immunohistochemical staining for Olig2, NogoA, AQP4 and Nestin was performed in combination with sequencing of IDH1 and IDH2 as well as promotor methylation analysis of the MGMT gene. Even though differences in overall survival according to Olig2 expression were observed, univariate and multivariate survival analysis did not reveal a firm significant prognostic impact of Olig2, NogoA, AQP4 or Nestin expression. Additionally, no differences in the expression of these markers depending on clinical status, age or gender were found. The established independent prognostic factors age<65, Karnofsky Performance Status> = 70 and methylated MGMT gene promoter were significant in the multivariate analysis. In conclusion expression of oligodendroglial and glioma stem cell markers do not have an independent prognostic effect in IDH-wildtype glioblastoma.
Topics: Adult; Aged; Aged, 80 and over; Aquaporin 4; Biomarkers, Tumor; Brain Neoplasms; Female; Glioblastoma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local; Nestin; Nogo Proteins; Oligodendrocyte Transcription Factor 2; Prognosis; Promoter Regions, Genetic; Retrospective Studies; Young Adult
PubMed: 32160197
DOI: 10.1371/journal.pone.0229274