Comprehensive profiling of myxopapillary ependymomas identifies a distinct molecular subtype with relapsing disease
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PROVIDER: PRJNA767016 | ENA |
REPOSITORIES: ENA
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Project description:BackgroundMyxopapillary ependymoma (MPE) is a heterogeneous disease regarding histopathology and outcome. The underlying molecular biology is poorly understood, and markers that reliably predict the patients' clinical course are unknown.MethodsWe assembled a cohort of 185 tumors classified as MPE based on DNA methylation. Methylation patterns, copy number profiles, and MGMT promoter methylation were analyzed for all tumors, 106 tumors were evaluated histomorphologically, and RNA sequencing was performed for 37 cases. Based on methylation profiling, we defined two subtypes MPE-A and MPE-B, and explored associations with epidemiological, clinical, pathological, and molecular characteristics of these tumors.ResultsMPE-A occurred at a median age of 27 years and were enriched with tumors demonstrating papillary morphology and MGMT promoter hypermethylation. Half of these tumors could not be totally resected, and 85% relapsed within 10 years. Copy number alterations were more common in MPE-A. RNA sequencing revealed an enrichment for extracellular matrix and immune system-related signatures in MPE-A. MPE-B occurred at a median age of 45 years and included many tumors with a histological diagnosis of WHO grade II and tanycytic morphology. Patients within this subtype had a significantly better outcome with a relapse rate of 33% in 10 years (P = 3.4e-06).ConclusionsWe unraveled the morphological and clinical heterogeneity of MPE by identifying two molecularly distinct subtypes. These subtypes significantly differed in progression-free survival and will likely need different protocols for surveillance and treatment.
| S-EPMC9527524 | biostudies-literature
Project description:Myxopapillary ependymoma is a heterogeneous disease with respect to histopathology and clinical outcome. However, there are no diagnostic markers or clinical parameters that reliably predict the progression-free survival of the respective patients. We analyzed 185 tumors that classified as myxopapillary ependymoma based on global DNA methylation. Of these, 46 samples have been previously analyzed in GSE65362, GSE90496 or GSE109381. Using k-means clustering, our series split up into two distinct subtypes: MPE-A occurred in younger patients (median age 27 years) and were significantly enriched with tumors demonstrating papillary morphology and MGMT promoter methylation. Half of these tumors could not be totally resected, and 85% relapsed within 10 years. On the other hand, MPE-B occurred at a median age of 45 years. They included a significantly higher number of tumors with an initial diagnosis of WHO grade II and tanycytic morphology. Importantly, patients within this subgroup had a significantly better outcome with a relapse rate of only 33% in 10 years.
2022-04-25 | GSE184900 | GEO
Project description:Across-species comprehensive copy number analyses identifies subtype-specific drivers of breast cancer development
| PRJNA227098 | 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:This study investigates the epigenetic and genetic landscape of a rare case of supratentorial ependymoma (ST-EPN), characterised by a novel TEAD1::NCOA2 fusion, expanding the molecular understanding of YAP1 fusion-positive ependymomas. Using Illumina methylation arrays, we performed DNA methylation profiling to classify the tumour subtype. (Additionally, RNA sequencing identified the TEAD1::NCOA2 fusion, implicating the activation of the HIPPO-YAP/TAZ pathway. These findings highlight the complexity of central nervous system tumour classifications and demonstrate the utility of advanced molecular diagnostics in cases where conventional methods, such as fluorescence in situ hybridisation (FISH), yield inconclusive results.)
2025-02-22 | E-MTAB-14789 | biostudies-arrayexpress
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: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