Similar Datasets
Project description:Diagnosis of glioma into the hierarchy of human brain development would greatly facilitate mechanistic studies and clinical services in combating glioma. By analysing the multi-dimension big data of glioma genome and clinical manifestations, we have recently developed an EM/PM classification scheme anchored in the brain development and glioma pathogenesis (Sun et al., PNAS 111:3538-3543, 2014). To translate the EM/PM classification into a clinical diagnostic tool, we here designed and validated a TaqMan low-density RT-PCR array (TLDA) and a support vector machine (SVM) based prediction model that enables individual diagnosis of gliomas into the EM/PM subtype with high accuracy and precision. Results of 153 individually diagnosed adult diffuse gliomas of WHO grades II-IV derived from Chinese or Swedish patients confirmed our previous data base investigations: EM and PM gliomas show distinct prognosis, occur at different ages, and harbor mutually exclusive patterns of genomic alterations detected by Sanger sequencing and shallow-coverage whole genome sequencing (WGS). Further, we show that shallow-coverage WGS enabled a systematic identification of clonal and subclonal copy number variations (CNV) in glioma genomes, and the extent and the pattern of CNV can serve as an objective marker of tumor progression in the PM gliomas harboring IDH mutations.
2019-05-16 | GSE131273 | GEO
Project description:Diagnosis of glioma into the hierarchy of human brain development would greatly facilitate mechanistic studies and clinical services in combating glioma. By analysing the multi-dimension big data of glioma genome and clinical manifestations, we have recently developed an EM/PM classification scheme anchored in the brain development and glioma pathogenesis (Sun et al., PNAS 111:3538-3543, 2014). To translate the EM/PM classification into a clinical diagnostic tool, we here designed and validated a TaqMan low-density RT-PCR array (TLDA) and a support vector machine (SVM) based prediction model that enables individual diagnosis of gliomas into the EM/PM subtype with high accuracy and precision. Results of 153 individually diagnosed adult diffuse gliomas of WHO grades II-IV derived from Chinese or Swedish patients confirmed our previous data base investigations: EM and PM gliomas show distinct prognosis, occur at different ages, and harbor mutually exclusive patterns of genomic alterations detected by Sanger sequencing and shallow-coverage whole genome sequencing (WGS). Further, we show that shallow-coverage WGS enabled a systematic identification of clonal and subclonal copy number variations (CNV) in glioma genomes, and the extent and the pattern of CNV can serve as an objective marker of tumor progression in the PM gliomas harboring IDH mutations.
2019-05-21 | GSE131464 | GEO
Project description:Individual Assignment of Adult Diffuse Gliomas into the EM/PM Molecular Subtypes
| PRJNA543775 | ENA
Project description:Individual Assignment of Adult Diffuse Gliomas into the EM/PM Molecular Subtypes Using a TaqMan Low-Density Array [Human Clariom D array]
| PRJNA543103 | ENA
Project description:Individual Assignment of Adult Diffuse Gliomas into the EM/PM Molecular Subtypes Using a TaqMan Low-Density Array [Taqman Low Density Array]
| PRJNA543777 | ENA
Project description:Molecular characterization of diffuse gliomas has thus far largely focused on genomic and transcriptomic interrogations. Here, we utilized mass spectrometry and overlay protein-level information onto genomically defined cohorts of diffuse gliomas to improve our downstream molecular understanding of these lethal malignancies. Bulk and macrodissected tissues were utilized to quantitate 5,496 unique proteins over three glioma cohorts subclassified largely based on their IDH and 1p19q codeletion status (IDH wild type (IDHwt), n = 7; IDH mutated (IDHmt), 1p19q non-codeleted, n = 7; IDH mutated, 1p19q-codeleted, n = 10). Clustering analysis highlighted proteome and systems-level pathway differences in gliomas according to IDH and 1p19q-codeletion status, including 287 differentially abundant proteins in macrodissection-enriched tumor specimens. IDHwt tumors were enriched for proteins involved in invasiveness and epithelial to mesenchymal transition (EMT), while IDHmt gliomas had increased abundances of proteins involved in mRNA splicing. Finally, these abundance changes were compared with IDH-matched GBM stem-like cells (GSCs) to better pinpoint protein patterns enriched in putative cellular drivers of gliomas. Using this integrative approach, we outline specific proteins involved in chloride transport (e.g. chloride intracellular channel 1, CLIC1) and EMT (e.g. procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, PLOD3, and serpin peptidase inhibitor clade H member 1, SERPINH1) that showed concordant IDH-status-dependent abundance differences in both primary tissue and purified GSC cultures. Given the downstream position proteins occupy in driving biology and phenotype, understanding the proteomic patterns operational in distinct glioma subtypes could help propose more specific, personalized, and effective targets for the management of patients with these aggressive malignancies.
| S-EPMC6773564 | biostudies-literature
Project description:BackgroundDNA methylation profiling has facilitated and improved the classification of a wide variety of tumors of the central nervous system. In this study, we investigated the potential utility of DNA methylation profiling to achieve molecular diagnosis in adult primary diffuse lower-grade glioma (dLGG) according to WHO 2016 classification system. We also evaluated whether methylation profiling could provide improved molecular characterization and identify prognostic differences beyond the classical histological WHO grade together with IDH mutation status and 1p/19q codeletion status. All patients diagnosed with dLGG in the period 2007-2016 from the Västra Götaland region in Sweden were assessed for inclusion in the study.ResultsA total of 166 dLGG cases were subjected for genome-wide DNA methylation analysis. Of these, 126 (76%) were assigned a defined diagnostic methylation class with a class prediction score ≥ 0.84 and subclass score ≥ 0.50. The assigned methylation classes were highly associated with their IDH mutation status and 1p/19q codeletion status. IDH-wildtype gliomas were further divided into subgroups with distinct molecular features.ConclusionThe stratification of the patients by methylation profiling was as effective as the integrated WHO 2016 molecular reclassification at predicting the clinical outcome of the patients. Our study shows that DNA methylation profiling is a reliable and robust approach for the classification of dLGG into molecular defined subgroups, providing accurate detection of molecular markers according to WHO 2016 classification.
| S-EPMC8091784 | biostudies-literature
Project description:Diffuse gliomas are among the most common adult central nervous system tumors with an annual incidence of more than 16,000 cases in the United States. Until very recently, the diagnosis of these tumors was based solely on morphologic features, however, with the publication of the WHO Classification of Tumours of the Central Nervous System, revised 4th edition in 2016, certain molecular features are now included in the official diagnostic and grading system. One of the most significant of these changes has been the division of adult astrocytomas into IDH-wildtype and IDH-mutant categories in addition to histologic grade as part of the main-line diagnosis, although a great deal of heterogeneity in the clinical outcome still remains to be explained within these categories. Since then, numerous groups have been working to identify additional biomarkers and prognostic factors in diffuse gliomas to help further stratify these tumors in hopes of producing a more complete grading system, as well as understanding the underlying biology that results in differing outcomes. The field of neuro-oncology is currently in the midst of a "molecular revolution" in which increasing emphasis is being placed on genetic and epigenetic features driving current diagnostic, prognostic, and predictive considerations. In this review, we focus on recent advances in adult diffuse glioma biomarkers and prognostic factors and summarize the state of the field.
| S-EPMC7408495 | biostudies-literature
Project description:BackgroundDiffuse gliomas in the adult population are the most common primary central nervous system (CNS) tumors. The World Health Organization incorporated isocitrate dehydrogenase (IDH) mutations and 1p/19q co-deletion with histopathological features into an "integrated diagnosis" in the revised classification of tumors of CNS. These molecular subgroups of diffuse gliomas are found to stratify patients into prognostically distinct groups better than the histological classification. The objectives of the current study were to assess the frequency of IDH mutation, ATRX expression loss, p53 overexpression, and 1p/19q co-deletion detection in adult diffuse gliomas (Grade II, III, and IV) and to correlate them with clinicopathological and histopathological features.Materials and methodsThe current study was a tertiary care hospital-based retrospective case series of 112 cases of adult diffuse gliomas. Immunohistochemistry (IHC)-based molecular detection was performed for IDH-1, ATRX, and p53 and fluorescent in situ hybridization (FISH) was performed for 1p/19q co-deletion detection.ResultsIDH-1 mutation was present in 30.4% (n = 34/112) cases, ATRX expression was lost in 18% (n = 19/104) cases, p53 was mutated in 39.3% (n = 42/107) cases and 1p19q was co-deleted in 25% (n = 4/16) cases. In the IDH1 mutant cases, with retained ATRX, FISH for 1p/19q co-deletion was performed and was co-deleted in four cases.ConclusionThe results of the present study indicate that IHC including IDH1/2, ATRX, and p53 is useful for the molecular classification of diffuse gliomas, which could be useful for the evaluation of prognosis, especially Grade III and II. Although the immunohistochemical approach does not replace genetic testing completely, it is a practical and powerful means of assessing molecular genetic changes. IDH mutations are the established markers of better prognosis in diffuse gliomas.
| S-EPMC8531577 | biostudies-literature
Project description:Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation in SETD2 (n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive with H3F3A K27M mutation (n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function including TP53 mutation (n = 9), PPM1D mutation (n = 2), and a novel type of PPM1D fusion (n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those with H3F3A mutations were categorized in the "RTK I (PDGFRA)" group, and those DCGs had a gene expression signature that was highly associated with PDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brain regions, promoter methylation of transcription factors genes associated with glial development showed a characteristic pattern presumably reflecting their tumor origin. Notably, SOX10, a key transcription factor associated with oligodendroglial differentiation and PDGFRA regulation, was up-regulated in both DCG and H3 K27M-mutant diffuse midline glioma, suggesting their developmental and biological commonality. In contrast, SOX10 was silenced by promoter methylation in most cerebral gliomas. These findings may suggest potential tailored targeted therapy for gliomas according to their brain region, in addition to providing molecular clues to identify the region-related cellular origin of DCGs.
| S-EPMC5663812 | biostudies-other