Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273777 | ENA |
REPOSITORIES: ENA
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Project description:Ependymal tumors across age groups have been classified solely by histopathology. It is, however, commonly accepted that this classification has limited clinical utility based on its poor reliability. We aimed at establishing a reliable and reproducible molecular classification using DNA methylation fingerprints of the tumors. Studying a cohort of 500 tumors allowed for the delineation of nine robust molecular subgroups, three in each anatomic compartment of the central nervous system (CNS). Two of the supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification by far and thus might serve as a basis for the upcoming update of the WHO classification of CNS tumors. DNA methylation patterns in tumors have been shown to represent a very stable molecular memory of the respective cell of origin throughout the disease course, thus making them particularly suitable for tumor classification purposes. Methylation fingerprinting of a large series of ependymal tumors of all grades revealed a highly reliable way of classifying this clinically extremely heterogeneous group of malignancies. In fact, out of nine highly reproducible molecular subgroups identified in the supratentorial, infratentorial and spinal regions, only two harbor the vast majority of clinical high-risk patients (mostly children) for whom novel therapeutic concepts are desperately needed. Since this analysis can be performed from minute amounts of DNA extracted from archived material, it is ideally suited for routine clinical application. We investigated a set of 562 ependymal tumors using the Illumina 450k methylation array.
2015-05-21 | E-GEOD-65362 | biostudies-arrayexpress
Project description:Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.
2015-05-21 | GSE65362 | GEO
Project description:Spinal intramedullary tumors comprise a heterogeneous group of entities with diverse histopathological features, making their diagnosis particularly challenging. In this study, we identified three cases of spinal ependymal tumors exhibiting a methylation profile of spinal (SP-) subependymoma (SEPN). One case exhibited histopathological features and a methylation profile typical of SP-SEPN, whereas the other two cases occurred in elderly patients and demonstrated circumscribed growth consistent with low-grade ependymal tumors; however, these tumors did not exhibit the typical histopathological features required for a diagnosis of SEPN in the 2021 WHO classification of CNS tumors, showing indistinct cluster formation, an astrocytic immunohistochemical profile suggested by Olig2 expression, and relatively elevated Ki-67 labeling indices of 4.5% and 3.1%. At the molecular level, both cases harbored telomerase reverse transcriptase promoter (pTERT) mutations and whole chromosome 7 gain. On two-dimensional t-distributed stochastic neighbor embedding analysis, both clustered within the SP-SEPN methylation class at its periphery, with low classifier calibration scores (0.70 and 0.69). According to the current WHO classification, one case in this study fulfills the diagnostic criteria for SP-SEPN, whereas the remaining two are designated as low-grade ependymal tumors (CNS WHO grade 2) with methylation profile of SP-SEPN because they do not meet the essential WHO histopathological criteria. Ependymal tumors exhibiting a methylation profile consistent with SEPN, but discordant histopathological features have been increasingly recognized, and the appropriate classification of such tumors remains a subject of ongoing debate. These cases provide important insights into the histopathological diversity of ependymal tumors and contribute to establishing a more comprehensive and systematic classification of ependymal tumors.
2026-08-26 | GSE319845 | GEO
Project description:Ependymal tumors across age groups have been classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patient outcome. We aimed at establishing a reliable molecular classification using DNA methylation fingerprints and gene expression data of the tumors on a large cohort of 500 tumors. Nine robust molecular subgroups, three in each anatomic compartment of the central nervous system (CNS), were identified. Total RNA from 209 ependymal tumor samples were hybridised to the Affymetrix HG U133 Plus 2.0 microarrays.
2015-05-21 | E-GEOD-64415 | biostudies-arrayexpress
Project description:Ependymal tumors across age groups have been classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patient outcome. We aimed at establishing a reliable molecular classification using DNA methylation fingerprints and gene expression data of the tumors on a large cohort of 500 tumors. Nine robust molecular subgroups, three in each anatomic compartment of the central nervous system (CNS), were identified.
2015-05-21 | GSE64415 | GEO
Project description:Meningiomas account for roughly one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system, there remains considerable uncertainty in predicting tumor behavior. Here we analyzed 160 tumors from all three WHO grades (I-III) using clinical, gene expression and sequencing data. Unsupervised clustering analysis identified three molecular groups that reliably predicted clinical severity. These groups did not directly correlate with the WHO grading system, which would classify more than half of the tumors in the most aggressive molecular group as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, resulting in cell cycle activation, and only tumors in this group tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.
2019-11-13 | GSE136661 | GEO
Project description:Ependymomas are neuroepithelial tumors of the central nervous system (CNS), presenting in both adults and children but accounting for almost 10% of all pediatric CNS tumors and up to 30% of CNS tumors in children under 3 years (Bouffet et al., 2009; McGuire et al., 2009; Rodriguez et al., 2009). In children, most ependymomas arise in the posterior fossa, while most adult ependymomas present around the lower spinal cord and spinal nerve roots. Ependymomas display a wide range of morphological features, and several variants are listed in the World Health Organization (WHO) classification (Ellison et al., 2016). These variants are assigned to three WHO grades (I-III), but the clinical utility of this classification is acknowledged to be limited (Ellison et al., 2011). An increasing understanding of the genomic landscape of ependymoma and the discovery of distinct molecular groups by DNA methylation or gene expression profiling have begun to refine approaches to disease classification and prognostication, but have yet to be translated into clinical routine (Hoffman et al., 2014; Mack et al., 2014; Pajtler et al., 2017; Pajtler et al., 2015; Parker et al., 2014; Wani et al., 2012; Witt et al., 2011). Our comprehensive study of DNA methylation profiling across the entire disease demonstrated three molecular groups for each major anatomic compartment: supratentorial (ST), posterior fossa (PF), and spinal (SP) (Pajtler et al., 2015). In the ST compartment, two molecular groups (ST-EPN-RELA and ST-EPN-YAP1) align with tumors harboring specific genetic alterations, RELA and YAP1 fusion genes, which were initially discovered in a whole genome sequencing study (Parker et al., 2014). Among PF ependymomas, two of three molecular groups, PFA (PF-EPN-A) and PFB (PF-EPN-B), account for nearly all tumors; PF-SE tumors are rare, generally showing the morphology of a subependymoma (Pajtler et al., 2015). PFA tumors are found mainly in infants and young children (median age ≈ 3yrs) and have a relatively poor outcome, while PFB tumors are generally found in young adults (median age ≈ 30yrs) and are associated with a better prognosis (Pajtler et al., 2015; Witt et al., 2011). PFA tumors show few copy number alterations (CNAs), while PFB tumors harbor multiple CNAs that tend to affect entire chromosomes. While recurrent structural variants (SVs) are found in ST ependymomas, recurrent SVs or other mutations, such as single nucleotide variants (SNVs) and insertions or deletions (indels), have not been identified in PF ependymomas to date (Mack et al., 2014; Parker et al., 2014).
2018-06-26 | GSE104210 | GEO
Project description:Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease, marked by mesangial IgA1 immune-complex deposition and a multi-hit pathogenesis. The Oxford classification grades histopathological lesions such as endocapillary hypercellularity (E0 and E1), which are associated with disease severity and prognosis. Despite advances in single-cell and spatial transcriptomics, the molecular basis of endocapillary hypercellularity in human IgAN remains unclear. Spatial transcriptomic data obtained using the GeoMx DSP platform were analyzed to compare gene expression profiles across normal, E0, and E1 groups.
2025-12-02 | GSE311745 | GEO
Project description:This study aimed to validate the use of DNA methylation profiling in the classification of pediatric central nervous system (CNS) tumors within the Brazilian public healthcare system. A total of 16 tumor samples from pediatric patients previously diagnosed with medulloblastoma or ependymoma—the two most common CNS tumors in children—were analyzed. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue and processed using the Infinium MethylationEPIC BeadChip array (Illumina). Methylation data were interpreted using two versions of the DKFZ brain tumor classifier (v11b4 and v12.5) and compared to reference diagnoses established through routine histopathological and molecular analyses. The study was conducted at the largest public hospital complex in Latin America and reflects practical challenges and opportunities for implementing precision diagnostics in real-world, resource-limited healthcare settings.
2026-03-31 | E-MTAB-15074 | biostudies-arrayexpress
Project description:Tumors of the central nervous system are the most common solid neoplasia during human childhood, representing one of the leading causes of cancer-related mortality. Tumors that originate from astrocyte cells (astrocytoma) in the brain are the most frequently found. According to their histological and pathological features, these tumors are classified into four categories. However, recently an extra layer of molecular classification of the tumorigenesis-associated genes IDH1/2 and H3F3A has been incorporated into the classification guidelines. While mutations in H3F3A are exclusively found in a subtype of pediatric astrocytoma grade IV, mutations in IDH1/2 are very rare in children younger than 14 years old. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied however focusing on the study of the transcriptomic profile of the different grades of astrocytoma (including the additional layer of molecular classification) in pediatric populations are scarce. Therefore, we have profiled the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing.
2022-10-25 | GSE196694 | GEO