Molecular characteristics and improved survival prediction in a cohort of 2023 ependymomas
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PROVIDER: PRJNA1017468 | ENA |
REPOSITORIES: ENA
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Project description:The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular information. However, as the integrated approach is still novel and some molecular ependymoma subtypes are quite rare, few studies have correlated integrated pathology and clinical outcome, often focusing on small series of single molecular types. We collected data from 2023 ependymomas as classified by DNA methylation profiling, consisting of 1736 previously published and 287 unpublished methylation profiles. Methylation data and clinical information were correlated, and an integrated model was developed to predict progression-free survival. Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%, respectively. EPN-PFA harbored chromosome 1q gains and/or 6q losses as markers for worse survival. In supratentorial EPN-ZFTA, a combined loss of CDKN2A and B indicated worse survival, whereas a single loss did not. Twelve out of 200 EPN-ZFTA (6%) were located in the posterior fossa, and these tumors relapsed or progressed even earlier than supratentorial tumors with a combined loss of CDKN2A/B. Patients with MPE and PF-SE, generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 59% and 65%, respectively. For the prediction of the 5-year progression-free survival, Kaplan-Meier estimators based on the molecular subtype, a Support Vector Machine based on methylation, and an integrated model based on clinical factors, CNV data, and predicted methylation scores achieved balanced accuracies of 66%, 68%, and 73%, respectively. Excluding samples with low prediction scores resulted in balanced accuracies of over 80%.
2024-01-31 | GSE243240 | GEO
Project description:The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular information. However, as the integrated approach is still novel and some molecular ependymoma subtypes are quite rare, few studies have correlated integrated pathology and clinical outcome, often focusing on small series of single molecular types. We collected data from 2023 ependymomas as classified by DNA methylation profiling, consisting of 1736 previously published and 287 unpublished methylation profiles. Methylation data and clinical information were correlated, and an integrated model was developed to predict progression-free survival. Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%, respectively. EPN-PFA harbored chromosome 1q gains and/or 6q losses as markers for worse survival. In supratentorial EPN-ZFTA, a combined loss of CDKN2A and B indicated worse survival, whereas a single loss did not. Twelve out of 200 EPN-ZFTA (6%) were located in the posterior fossa, and these tumors relapsed or progressed even earlier than supratentorial tumors with a combined loss of CDKN2A/B. Patients with MPE and PF-SE, generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 59% and 65%, respectively. For the prediction of the 5-year progression-free survival, Kaplan-Meier estimators based on the molecular subtype, a Support Vector Machine based on methylation, and an integrated model based on clinical factors, CNV data, and predicted methylation scores achieved balanced accuracies of 66%, 68%, and 73%, respectively. Excluding samples with low prediction scores resulted in balanced accuracies of over 80%. In sum, our large-scale analysis of ependymomas provides robust information about molecular features and their clinical meaning. Our data are particularly relevant for rare and hardly explored tumor subtypes and seemingly benign variants that display higher recurrence rates than previously believed.
| S-EPMC10808151 | biostudies-literature
Project description:ImmuniT Platform for Improved Neoantigen Prediction in Lung Cancer
| PRJNA1311830 | ENA
Project description:Ependymomas are common childhood brain tumors that occur throughout the nervous system, but are most common in the pediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic SNVs. While devoid of recurrent SNVs and focal copy number aberrations, poor prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype (CIMP). Transcriptional silencing driven by CpG methylation converges exclusively on targets of the polycomb repressor complex 2 (PRC2) that represses expression of differentiation genes through tri-methylation of H3K27. CIMP-positive (CIMP+) hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically de-regulated but genetically bland. 10 primary posterior fossa ependymomas have been analyzed
2014-03-15 | E-GEOD-55920 | biostudies-arrayexpress
Project description:1) Illumina 450K methylation profiles-48 posterior fossa ependymomas
2014-03-25 | GSE45353 | GEO
Project description:Ependymomas are common childhood brain tumors that occur throughout the nervous system, but are most common in the pediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic SNVs. While devoid of recurrent SNVs and focal copy number aberrations, poor prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype (CIMP). Transcriptional silencing driven by CpG methylation converges exclusively on targets of the polycomb repressor complex 2 (PRC2) that represses expression of differentiation genes through tri-methylation of H3K27. CIMP-positive (CIMP+) hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically de-regulated but genetically bland.
2014-03-15 | GSE55920 | GEO
Project description:Improved Prediction of Smoking Status via Isoform-Aware RNA-seq Deep Learning Models
| PRJNA666220 | ENA
Project description:1) Illumina 450K methylation profiles-48 posterior fossa ependymomas NA
2014-03-25 | E-GEOD-45353 | biostudies-arrayexpress
Project description:We have discovered two major molecular subgroups of PFA molecular group posterior fossa ependymomas by DNA methylation profiling. These are also distinguished by gene expression profiling using Affymetrix U133v2 arrays with correspondence to data generated by DNA methylation profiling.
2018-08-03 | GSE100240 | GEO
Project description:Ependymomas are glial tumors that share morphologic similarities with ependymal cells. Here we laser microdissected ependymoma cells of 15 infratentorial tumors and generated gene expression profiles. These profiles were compared to those of 7 laser microdissected ependymal tissues. 10 000 laser microdissected cells of each of the 15 different infratentorial ependymomas and seven ependymal autopsy tissues were lysed and gene expression profiles were generated. Expression profiles of ependymomas were compared to those of ependymal cells.
2010-12-10 | E-GEOD-25604 | biostudies-arrayexpress