Concurrence of High-Grade Brainstem Glioma and Multiple Sclerosis

Hinnell, Claire; Almekhlafi, M; Joseph, Jeffrey T.; Bell, Robert B.; Sharma, Payal; Furtado, Sarah

doi:10.1017/s0317167100010556

Cited by 7 publications

(5 citation statements)

References 7 publications

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“…Human MTG cellular data, expression level, specificity, and diseases. (A) RNA-seq gene expression quantification with absolute expression levels estimated as counts per million (CPM) using exonic reads from [ 29 ]. (B) Cell type specificity was calculated based on the Tau-score (τ) defined in [ 30 ].…”

Section: Supporting Informationmentioning

confidence: 99%

“…(B) Cell type specificity was calculated based on the Tau-score (τ) defined in [ 30 ]. This measure has previously been employed using the same dataset [ 29 ]. Distribution of τ for brain disease associated, non-brain disease, and unassociated genes.…”

Section: Supporting Informationmentioning

confidence: 99%

“…Human and mouse EWCE distributions. (A) Aligned transcriptomic taxonomy of cell types in human MTG to 2 distinct mouse cortical areas, primary visual cortex (V1), and a premotor area, the anterior lateral motor cortex (ALM) from [ 29 ] allows comparison of cell type enrichments between species. Scatterplot of disease-subclass EWCE values for mouse and human colored by CTG 1–4.…”

Section: Supporting Informationmentioning

confidence: 99%

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A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases

et al. 2023

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Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular-based signature, based on differential co-expression, that is often unique to that disease. Brain diseases can be compared and aggregated based on the similarity of their signatures which often associates diseases from diverse phenotypic classes. Analysis of 40 common human brain diseases identifies 5 major transcriptional patterns, representing tumor-related, neurodegenerative, psychiatric and substance abuse, and 2 mixed groups of diseases affecting basal ganglia and hypothalamus. Further, for diseases with enriched expression in cortex, single-nucleus data in the middle temporal gyrus (MTG) exhibits a cell type expression gradient separating neurodegenerative, psychiatric, and substance abuse diseases, with unique excitatory cell type expression differentiating psychiatric diseases. Through mapping of homologous cell types between mouse and human, most disease risk genes are found to act in common cell types, while having species-specific expression in those types and preserving similar phenotypic classification within species. These results describe structural and cellular transcriptomic relationships of disease risk genes in the adult brain and provide a molecular-based strategy for classifying and comparing diseases, potentially identifying novel disease relationships.

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Section: Supporting Informationmentioning

confidence: 99%

Section: Supporting Informationmentioning

confidence: 99%

Section: Supporting Informationmentioning

confidence: 99%

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A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases

et al. 2023

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“…From an immunological perspective, both diseases comprise opposed paradigmatic conditions within the central nervous system (CNS), with excessive immune reactions causing multiple sclerosis and profound immunosuppression enabling glioma progression, respectively 26 – 28 . The role of underlying onco-immunological mechanisms for disease susceptibility and etiology has been repeatedly discussed without answering the question of an incidental co-existence or causal relationship 23 , 29 , 3 . In this context, epigenetic mechanisms could play an essential role.…”

Section: Discussionmentioning

confidence: 99%

Concurrent gliomas in patients with multiple sclerosis

Sahm,

Kessler,

Eisele

et al. 2023

Commun Med

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Background Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives. Methods A multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients. Results MS neither predisposes nor protects from the development of gliomas. Patients with glioblastoma WHO grade 4 without isocitratdehydrogenase (IDH) mutations have a longstanding history of MS, whereas patients diagnosed with IDH-mutant astrocytoma WHO grade 2 receive multiple sclerosis diagnosis mostly at the same time or later. Concurrent MS is associated with a lesser extent of tumor resection and a worse prognosis in IDH-mutant glioma patients (PFS 32 vs. 64 months, p = 0.0206). When assessing tumor-intrinsic differences no distinct subgroup-defining methylation pattern is identified in gliomas of MS patients compared to other glioma samples. However, differential methylation of immune-related genetic loci including human leukocyte antigen locus on 6p21 and interleukin locus on 5q31 is found in MS patients vs. matched non-MS patients. In line, inflammatory disease activity increases in 42% of multiple sclerosis patients after brain tumor radiotherapy suggesting a susceptibility of multiple sclerosis brain tissue to pro-inflammatory stimuli such as ionizing radiation. Conclusions Concurrent low-grade gliomas should be considered in multiple sclerosis patients with slowly progressive, expansive T2/FLAIR lesions. Our findings of typically reduced extent of resection in MS patients and increased MS activity after radiation may inform future treatment decisions.

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“…From an immunological perspective, both diseases comprise opposed paradigmatic conditions within the central nervous system (CNS), with excessive immune reactions causing multiple sclerosis and profound immunosuppression enabling glioma progression, respectively 25 26 27 . The role of underlying onco-immunological mechanisms for disease susceptibility and etiology has been repeatedly discussed without answering the question of an incidental co-existence or causal relationship 22 28 3 . In this context, epigenetic mechanisms could play an essential role.…”

Section: Discussionmentioning

confidence: 99%

Concurrent gliomas in patients with multiple sclerosis

Sahm

Keßler

Eisele

et al. 2022

Preprint

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Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives. A multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients. MS neither predisposes nor protects from the development of gliomas. Patients with glioblastoma WHO grade IV without IDH mutations had a longstanding history of MS, whereas patients diagnosed with IDH-mutant astrocytoma WHO grade II received multiple sclerosis diagnosis mostly at the same time or later. Concurrent MS was associated with a lesser extent of tumor resection and a worse prognosis in IDH-mutant glioma patients (PFS 32 vs. 64 months, p=0.0206). When assessing tumor-intrinsic differences no distinct subgroup-defining methylation pattern was identified in gliomas of MS patients compared to other glioma samples. However, differential methylation of immune-related genetic loci including human leukocyte antigen locus on 6p21 and interleukin locus on 5q31 was found in MS patients vs. matched non-MS patients. In line, inflammatory disease activity increased in 42% of multiple sclerosis patients after brain tumor radiotherapy suggesting a susceptibility of multiple sclerosis brain tissue to pro-inflammatory stimuli such as ionizing radiation. Concurrent low-grade gliomas should be considered in multiple sclerosis patients with slowly progressive, expansive T2/FLAIR lesions. Our findings of typically reduced extent of resection in MS patients and increased MS activity after radiation inform future treatment decisions.

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Concurrence of High-Grade Brainstem Glioma and Multiple Sclerosis

Cited by 7 publications

References 7 publications

A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases

A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases

Concurrent gliomas in patients with multiple sclerosis

Concurrent gliomas in patients with multiple sclerosis

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