Rasmussen＇s encephalitis （ RE ） , which was first described by Rasmussen in 1958 , is a rare, dispersed, and progressive neurological syndrome that is characterized by focal epilepsy, unilateral inflammation of the...Rasmussen＇s encephalitis （ RE ） , which was first described by Rasmussen in 1958 , is a rare, dispersed, and progressive neurological syndrome that is characterized by focal epilepsy, unilateral inflammation of the cerebral cortex, progressive hemiplegia and cognitive deterioration. The etiology of this syndrome remains under investigation, and it is hypothesized and widely accepted that RE is a T-cell-mediated autoimmune response. However, the antigenic epitopes and mechanisms are still unknown. The pathological characteristics of RE are cortical inflammation, neuronal loss, and gliosis that are confined to one cere-bral hemisphere. Hemispherectomy remains the only cure for the seizures and cognitive deterioration associated with the disease, but this procedure results in inevitable functional loss in the brain. Compared with surgery, immunomodulatory treatments are expected to cause less neurological deficits, but with limited clinical effect.展开更多
Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictl...Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.展开更多
文摘Rasmussen＇s encephalitis （ RE ） , which was first described by Rasmussen in 1958 , is a rare, dispersed, and progressive neurological syndrome that is characterized by focal epilepsy, unilateral inflammation of the cerebral cortex, progressive hemiplegia and cognitive deterioration. The etiology of this syndrome remains under investigation, and it is hypothesized and widely accepted that RE is a T-cell-mediated autoimmune response. However, the antigenic epitopes and mechanisms are still unknown. The pathological characteristics of RE are cortical inflammation, neuronal loss, and gliosis that are confined to one cere-bral hemisphere. Hemispherectomy remains the only cure for the seizures and cognitive deterioration associated with the disease, but this procedure results in inevitable functional loss in the brain. Compared with surgery, immunomodulatory treatments are expected to cause less neurological deficits, but with limited clinical effect.
基金supported by the National Natural Science Foundation of China(Nos.81773015 and 82072789)the National Key Research and Development Program of China(No.2019YFE0108100)the Erik Philip-Sörensen Foundation.
文摘Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
