Integrative Molecular Classification of Meningiomas
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ABSTRACT:
PROVIDER: EGAS00001004982 | EGA |
REPOSITORIES: EGA
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Project description:Hepatoblastoma (HB) is the predominant pediatric liver cancer with limited therapeutic options for patients with aggressive tumors. Nevertheless, it is a rare disease. Here, we performed a high-throughput molecular study of 32 patients with HB and major findings were validated in additional 80 cases. We unveiled an epigenetic footprint including downregulation of RNA-editing, hyperediting of the tumor suppressor BLCAP,14q32 DLK1-DIO3 locus overexpression, DNA hypomethylation and CpG island hypermethylation. Based on these findings, we defined an integrative molecular classification of HB that improve current clinical stratification, and identified CHKA as a therapeutic target for the poor prognostic subclass.
2020-03-23 | GSE132218 | GEO
Project description:Spinal meningiomas account for 1.2-12% of all meningiomas and 25-45% of all spinal tumours. About 20% of intracranial, but also 4.6% of spinal meningiomas recur and require additional treatment. The classification of intracranial meningiomas has evolved considerably in recent years and uses genetic [1,2,4] as well as epigenetic parameters [3,5] in order to more precisely predict the patients’ prognosis and to lay the ground for therapeutic regiments that are adapted to the aggressiveness of a patient’s tumor. On the other hand, spinal meningiomas are missing in many of the large cohorts that were gathered for the molecular profiling of meningiomas. Also, they have never been thoroughly analyzed separately, and their classification still relies on histopathological findings solely. We analysed 65 tumour samples from 63 patients, who had histologically proven spinal meningioma to perform genetic and epigenetic profiling. Clinical features are described in Supplementary Table 1, online resource. T-distributed Stochastic Neighbor Embedding (t-SNE) analysis of genome-wide DNA methylation data shows that most spinal meningiomas separate from cranial meningiomas (Fig. 1A&B) and form two distinct clusters.
2022-10-12 | GSE212449 | GEO
Project description:Hepatoblastoma (HB) is the predominant pediatric liver cancer with limited therapeutic options for patients with aggressive tumors. Nevertheless, it is a rare disease. Here, we performed a high-throughput molecular study of 32 patients with HB and major findings were validated in additional 80 cases. We unveiled an epigenetic footprint including downregulation of RNA-editing, hyperediting of the tumor suppressor BLCAP,14q32 DLK1-DIO3 locus overexpression, DNA hypomethylation and CpG island hypermethylation. Based on these findings, we defined an integrative molecular classification of HB that improve current clinical stratification, and identified CHKA as a therapeutic target for the poor prognostic subclass.
2020-03-23 | GSE132037 | GEO
Project description:Hepatoblastoma (HB) is the predominant pediatric liver cancer with limited therapeutic options for patients with aggressive tumors. Nevertheless, it is a rare disease. Here, we performed a high-throughput molecular study of 32 patients with HB and major findings were validated in additional 80 cases. We unveiled an epigenetic footprint including downregulation of RNA-editing, hyperediting of the tumor suppressor BLCAP,14q32 DLK1-DIO3 locus overexpression, DNA hypomethylation and CpG island hypermethylation. Based on these findings, we defined an integrative molecular classification of HB that improve current clinical stratification, and identified CHKA as a therapeutic target for the poor prognostic subclass.
2020-03-23 | GSE133039 | GEO
Project description:Hepatoblastoma (HB) is the predominant pediatric liver cancer with limited therapeutic options for patients with aggressive tumors. Nevertheless, it is a rare disease. Here, we performed a high-throughput molecular study of 32 patients with HB and major findings were validated in additional 80 cases. We unveiled an epigenetic footprint including downregulation of RNA-editing, hyperediting of the tumor suppressor BLCAP,14q32 DLK1-DIO3 locus overexpression, DNA hypomethylation and CpG island hypermethylation. Based on these findings, we defined an integrative molecular classification of HB that improve current clinical stratification, and identified CHKA as a therapeutic target for the poor prognostic subclass.
2020-07-09 | GSE132399 | GEO
Project description:Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.
| S-EPMC11604310 | biostudies-literature
Project description:Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications
| PRJNA546530 | ENA
Project description:RNA-sequencing of meningiomas for integrative molecular classification.
| EGAD00001007494 | EGA
Project description:Meningiomas represent one of the most common and clinically heterogeneous brain tumor types that only modestly correlate with histopathologic features. While emerging molecular profiling efforts have linked specific genomic drivers to distinct clinical patterns, the proteomic landscape of meningiomas remains largely unexplored. We utilize mass spectrometry to profile a clinically well-annotated cohort (n=69) of meningiomas stratified to span all three World Health Organization (WHO) grades and various degrees of clinical aggressiveness. In total, we quantify 3042 unique proteins and compare the patterns across different clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic (n=106 proteins, Welch’s t-test, P<0.01) and pathway-level (e.g. Notch and PI3K/AKT/mTOR) differences between convexity and skull base meningiomas. Supervised comparative analyses of different pathological grades revealed distinct patterns between benign (WHO Grade I) and atypical/malignant (WHO Grade II and III) meningiomas with classic oncogenes often enriched in higher grade lesions. Independent of WHO grade, clinically aggressive meningiomas, that rapidly recurred, also had distinctive protein patterns that converged on mRNA processing and impaired activation of the extracellular matrix naba matrisome complex. Larger sized meningiomas, and those with previous radiation exposure, also had distinct protein profiles. Collectively, we highlight distinct clinically-dependent proteomic patterns of meningiomas that may help better predict outcome and guide the development of more personalized and directed therapies.
2019-05-30 | PXD012923 | Pride
Project description:Single-nucleus RNA-sequencing of meningiomas for integrative molecular classification
| EGAD00001007677 | EGA