Correction to: Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma

Haage, Verena; Semtner, Marcus; Vidal, Ramón; Hernández, Daniel; Pong, Winnie W.; Chen, Zhihong; Hambardzumyan, Dolores; Magrini, Vincent; Ly, Amy; Walker, Jason; Mardis, Elaine R.; Mertins, Philipp; Sauer, Sascha; Kettenmann, Helmut; Gutmann, David H.

doi:10.1186/s40478-019-0875-3

Cited by 60 publications

(77 citation statements)

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“…From 2013–2017 in the United States, the incidence of brain and other nervous system cancers in patients aged 0–19 was 3.2 per 100,000 [ 56 ]. Pediatric gliomas, including pilocytic astrocytoma, are the most common type of pediatric brain tumour [ 90 , 91 ].…”

Section: Gliomamentioning

confidence: 99%

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients

et al. 2021

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Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.

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Section: Gliomamentioning

confidence: 99%

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients

et al. 2021

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“…NDUFB5 or nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 beta subcomplex 5, is a nuclear-encoded mitochondrial protein which functions as part of complex 1 of the electron transport chain. Many studies have shown NDUFB5 levels is altered in disease, typically coupled with altered expression of other mitochondrial respiratory proteins [ 63 , 64 , 65 , 66 ]. In the context of AD, NDUFB5 has been suggested as a hub protein associated with disease pathogenesis based on co-expression analyses [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy

Koren

Hamm

Cloyd

et al. 2021

IJMS

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Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human Alzheimer’s disease (AD) proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence candidate proteins as novel therapeutically relevant targets for the treatment of tauopathy. Proteomics data are available via ProteomeXchange with identifier PXD023562.

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“…Of the studies used, 55% utilized microarray experiments, 40% used RNA sequencing and 5% were based on single cell RNA sequencing experiments. In total, transcriptomic data of 39 studies was acquired [ 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 ].…”

Section: Methodsmentioning

confidence: 99%

Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale

Ruffini

Klingenberg

Schweiger

et al. 2020

Cells

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Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies have suggested relations between neurodegenerative diseases for many years (e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways). We gathered publicly available genomic, transcriptomic, and proteomic data from 177 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases on three analyzed omics-layers. The results show a remarkably high number of shared differentially expressed genes between the transcriptomic and proteomic levels for all conditions, while showing a significant relation between genomic and proteomic data between AD and PD and AD and ALS. We identified a set of 139 genes being differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented gene ontology (GO) Terms involved in the development of neurodegeneration, such as response to heat and hypoxia, positive regulation of cytokines and angiogenesis, and RNA catabolic process. Furthermore, the four analyzed neurodegenerative diseases (NDDs) were clustered by their mean direction of regulation throughout all transcriptomic studies for this set of 139 genes, with the closest relation regarding this common gene set seen between AD and HD. GO-Term and pathway analysis of the proteomic overlap led to biological processes (BPs), related to protein folding and humoral immune response. Taken together, we could confirm the existence of many relations between Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis on transcriptomic and proteomic levels by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection and the striking relation of the results to processes leading to neurodegeneration between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring many studies simultaneously, including multiple omics-layers of different neurodegenerative diseases simultaneously, holds new relevant insights that do not emerge from analyzing these data separately. Furthermore, the results shed light on processes like the humoral immune response that have previously been described only for certain diseases. Our data therefore suggest human patients with neurodegenerative diseases should be addressed as complex biological systems by integrating multiple underlying data sources.

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Correction to: Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma

Abstract: The original publication of this article [1] contained 3 minor errors in Figs. 1, 3 and 5. In this correction article the updated figures are published. The figure captions describe the updated information in these figures.

Cited by 60 publications

References 1 publication

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy

Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale

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