Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Christopher Stephen
PROVIDER: S-ECPF-GEOD-27279 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients.
| S-EPMC4154494 | biostudies-literature
Project description:Despite histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymomas reveals the existence of two demographically, transcriptionally, genetically and clinically distinct groups of posterior fossa (PF) ependymoma. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis, and death as compared to Group B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third group of independent ependymomas using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. This SuperSeries is composed of the following subset Series: GSE27283: Human ependymoma samples [expression] GSE27286: Human ependymoma samples, Subgrouping [aCGH - German Cancer Research Center human 33K BAC array] Refer to individual Series
2011-08-14 | E-GEOD-27287 | biostudies-arrayexpress
Project description:Gene expression (mRNA) profiling of human ependymomas Despite the histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymoma. Group-A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, secondary metastasis, and death as compared to Group-B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third independent group of tumors using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. We analyzed 102 primary ependymomas on the Affymetrix Exon 1.0ST platform (Gene Level).
2011-08-14 | E-GEOD-27279 | biostudies-arrayexpress
Project description:Despite histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymomas reveals the existence of two demographically, transcriptionally, genetically and clinically distinct groups of posterior fossa (PF) ependymoma. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis, and death as compared to Group B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third group of independent ependymomas using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. This SuperSeries is composed of the SubSeries listed below.
2011-08-15 | GSE27287 | GEO
Project description:Gene expression (mRNA) profiling of human ependymomas Despite the histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymoma. Group-A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, secondary metastasis, and death as compared to Group-B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third independent group of tumors using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients.
2011-08-15 | GSE27279 | GEO
Project description:BackgroundThe risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB.MethodsWe extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers.ResultsFor all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86.ConclusionsWe present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
| S-EPMC9159456 | biostudies-literature
Project description:BackgroundPosterior fossa ependymoma (PFE) comprises 2 groups, PF group A (PFA) and PF group B (PFB), with stark differences in outcome. However, to the authors' knowledge, the long-term outcomes of PFA ependymoma have not been described fully. The objective of the current study was to identify predictors of survival and neurocognitive outcome in a large consecutive cohort of subgrouped patients with PFE over 30 years.MethodsDemographic, survival, and neurocognitive data were collected from consecutive patients diagnosed with PFE from 1985 through 2014 at the Hospital for Sick Children in Toronto, Ontario, Canada. Subgroup was assigned using genome-wide methylation array and/or immunoreactivity to histone H3 K27 trimethylation (H3K27me3).ResultsA total of 72 PFE cases were identified, 89% of which were PFA. There were no disease recurrences noted among patients with PFB. The 10-year progression-free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%-53.1%). Analysis of consecutive 10-year epochs revealed significant improvements in progression-free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full-scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (-1.33 ± 0.42 points/year; P = .0042).ConclusionsData from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time.
| S-EPMC6508980 | biostudies-literature
Project description:Genomewide DNA methylation array profiling of nine posterior fossa ependymomas harboring activating mutations in ACVR1. Two samples clustered with the PFA subtype and demonstrated H3K27me3 loss by immunohistochemistry, while the remaining 7 showed retained H3K27me3 and formed a methylation cluster distinct from other ependymal tumors. For these previsouly unpublished cases, the Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue.
2022-05-01 | GSE196013 | GEO
Project description:BACKGROUND:5-Hydroxymethylcytosine (5hmC) is a novel epigenetic mark and may be involved in the mechanisms of tumorigenesis and malignant transformation. However, the role of 5hmC in ependymoma, the third most common brain tumor in children, remains unclear. The aim of this study sought to identify the characterization of 5hmC levels in pediatric posterior fossa ependymoma and to evaluate whether 5hmC levels could be a potential factor to predict clinical outcomes. RESULTS:Our results showed that 5hmC levels were globally decreased in posterior fossa ependymoma compared with normal cerebellum tissues (P < 0.001). Group A posterior fossa ependymomas had higher 5hmC levels than group B tumors (P = 0.007). Moreover, 5hmC levels positively correlated with Ki-67 index in posterior fossa ependymoma (r = 0.428, P = 0.003). Multivariate Cox hazards model revealed that patients with high 5hmC levels (>?0.102%) had worse PFS and OS than patients with lower 5hmC levels (<?0.102%) (PFS: HR = 3.014; 95% CI, 1.040-8.738; P = 0.042; OS: HR = 2.788; 95% CI, 0.974-7.982; P = 0.047). CONCLUSIONS:Our findings suggest that loss of 5hmC is an epigenetic hallmark for pediatric posterior fossa ependymoma. 5hmC levels may represent a potential biomarker to predict prognosis in children with posterior fossa ependymoma.
| S-EPMC6988368 | biostudies-literature
Project description:PurposeImaging descriptions of posterior fossa ependymoma in children have focused on magnetic resonance imaging (MRI) signal and local anatomic relationships with imaging location only recently used to classify these neoplasms. We developed a quantitative method for analyzing the location of ependymoma in the posterior fossa, tested its effectiveness in distinguishing groups of tumors, and examined potential associations of distinct tumor groups with treatment and prognostic factors.MethodsPre-operative MRI examinations of the brain for 38 children with histopathologically proven posterior fossa ependymoma were analyzed. Tumor margin contours and anatomic landmarks were manually marked and used to calculate the centroid of each tumor. Landmarks were used to calculate a transformation to align, scale, and rotate each patient's image coordinates to a common coordinate space. Hierarchical cluster analysis of the location and morphological variables was performed to detect multivariate patterns in tumor characteristics. The ependymomas were also characterized as "central" or "lateral" based on published radiological criteria. Therapeutic details and demographic, recurrence, and survival information were obtained from medical records and analyzed with the tumor location and morphology to identify prognostic tumor characteristics.ResultsCluster analysis yielded two distinct tumor groups based on centroid location The cluster groups were associated with differences in PFS (p = .044), "central" vs. "lateral" radiological designation (p = .035), and marginally associated with multiple operative interventions (p = .064).ConclusionsPosterior fossa ependymoma can be objectively classified based on quantitative analysis of tumor location, and these classifications are associated with prognostic and treatment factors.
| S-EPMC4967400 | biostudies-literature