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European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Molecular Biology Reports Dec 2020The mitochondrial encephalomyopathies represent a clinically heterogeneous group of neurodegenerative disorders. The clinical phenotype of patients could be explained by... (Review)
Review
The mitochondrial encephalomyopathies represent a clinically heterogeneous group of neurodegenerative disorders. The clinical phenotype of patients could be explained by mutations of mitochondria-related genes, notably SUCLG1 and SUCLA2. Here, we presented a 5-year-old boy with clinical features of mitochondrial encephalomyopathy from Iran. Also, a systematic review was performed to explore the involvement of SUCLG1 mutations in published mitochondrial encephalomyopathies cases. Genotyping was performed by implementing whole-exome sequencing. Moreover, quantification of the mtDNA content was performed by real-time qPCR. We identified a novel, homozygote missense variant chr2: 84676796 A > T (hg19) in the SUCLG1 gene. This mutation substitutes Cys with Ser at the 60-position of the SUCLG1 protein. Furthermore, the in-silico analysis revealed that the mutated position in the genome is well conserved in mammalians, that implies mutation in this residue would possibly result in phenotypic consequences. Here, we identified a novel, homozygote missense variant chr2: 84676796 A > T in the SUCLG1 gene. Using a range of experimental and in silico analysis, we found that the mutation might explain the observed phenotype in the family.
Topics: Child, Preschool; DNA, Mitochondrial; Homozygote; Humans; Iran; Male; Mitochondria; Mitochondrial Encephalomyopathies; Mutation, Missense; Succinate-CoA Ligases
PubMed: 33230783
DOI: 10.1007/s11033-020-05999-y -
Expert Review of Clinical Immunology Oct 2020The tripartite motif (TRIM) plays various roles in pathological and physiological functions, including neurological diseases, genetic disorders, carcinogenesis, innate...
INTRODUCTION
The tripartite motif (TRIM) plays various roles in pathological and physiological functions, including neurological diseases, genetic disorders, carcinogenesis, innate immune signaling, and antiviral activity. TRIM56 is a cytoplasmic protein whose expression is stimulated by type I interferon and may function as an antiviral agent. Here, the authors conducted a systematic search on papers that reported antiviral effects of TRIM56.
AREAS COVERED
The authors conducted a comprehensive search of the PubMed database without time or language limitation, after using the Medical Subject Headings (MeSH) Database terms. Initially, a structured search and full article review yielded 31 papers. Relevant original and review articles on TRIM56 were included. The reference lists were then reviewed, and the cited articles were added. : TRIM56 has been shown to have direct antiviral actions against positive-sense single-stranded RNA viruses from the families , and . Moreover, it may be effective against negative-sense single-strand RNA viruses from the families and , as well as a DNA virus, Herpes simplex virus 1 (HSV-1). These studies could suggest the potential of a TRIM56-based antiviral against COVID-19 from the family , containing single-stranded positive-sense RNA genome. However, its efficacy and antiviral mechanisms need to be further examined.
Topics: Animals; Antiviral Agents; COVID-19; Humans; RNA Viruses; SARS-CoV-2; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 32903131
DOI: 10.1080/1744666X.2020.1822168 -
Medicine Nov 2019Dysregulated circular RNAs have been implicated in the pathogenesis of cancer. Recent studies indicate that has_circ_0001649 lowly expressed in multiple types of cancer.... (Meta-Analysis)
Meta-Analysis
SNF2 histone linker PHD RING helicase related Has_circ_0001649 as a diagnostic and prognostic biomarker in solid cancer: A PRISMA-compliant meta-analysis based on the Chinese population.
BACKGROUND
Dysregulated circular RNAs have been implicated in the pathogenesis of cancer. Recent studies indicate that has_circ_0001649 lowly expressed in multiple types of cancer. The purpose of this study is to investigate the roles of has_circ_0001649 as a diagnostic and prognostic marker for Chinese patients with cancer.
METHODS
Adhering to preferred reporting items for systematic reviews and meta-analyses guidelines, systematic literature searches were performed using Pubmed, Embase, and the web of Science to retrieve articles fulfilled all inclusion criteria. The significance of has_circ_0001649 in diagnosis and prognosis of cancer patients were evaluated. Meta-Disc 1. 4 and STATA 12. 0 were used to analyze the data from collected studies.
RESULTS
Eleven articles with 761 patients were included in present meta-analysis, of which 4 were about diagnosis, 5 were about prognosis, and 6 were about tumor differentiation grade. For the diagnostic value of has_circ_0001649, the pooled results for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with their 95% confidential intervals were 0. 78 (0. 73-0. 83), 0. 75 (0. 70-0. 80), 3. 17 (2. 56-3. 93), 0. 29 (0. 23-0. 36), and 11. 41 (7. 80-16. 7), respectively. The area under the curve of summary receiver operator characteristic was 0.8408 (Q = 0. 7725). Meanwhile, the result showed no obvious publication bias in this analysis for the P-value of Deeks' test was .489. For the prognostic value, the pooled hazard ratio for overall survival was 0.45 (0.324-0.626). Lower expression of has_circ_0001649 was also prone to lower tumor differentiation grade (odds ratio = 2.58, P < .0001).
CONCLUSIONS
Has_circ_0001649 could be used as a potential biomarker for diagnosis and prognosis in solid cancer. Further prospective studies are required to validate its clinical application.
Topics: Asian People; Biomarkers, Tumor; China; DNA Helicases; Humans; Neoplasm Grading; Neoplasms; Odds Ratio; Prognosis; RNA, Circular; ROC Curve; Sensitivity and Specificity; Ubiquitin-Protein Ligases
PubMed: 31689751
DOI: 10.1097/MD.0000000000017488