-
Advances in Therapy Jan 2022The canonical isocitrate dehydrogenase 1 R132 mutation (IDH1 R132) is the most frequent mutation among IDH-mutated gliomas. Non-canonical IDH1 mutations or IDH2... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The canonical isocitrate dehydrogenase 1 R132 mutation (IDH1 R132) is the most frequent mutation among IDH-mutated gliomas. Non-canonical IDH1 mutations or IDH2 mutations are unusual and their clinical and biological role is still unclear.
METHODS
We performed a systematic review and meta-analysis to assess the clinical role of IDH non-canonical mutations.
RESULTS
Overall, we selected 13 of 3513 studies reporting data of 4007 patients with a diagnosis of grade 2 and grade 3 glioma including 3091 patients with a molecularly proven IDH1 or IDH2 mutation. Patients with non-canonical IDH1 mutations were younger and presented a higher DNA methylation level as compared to those with canonical IDH1 R132H alteration. The overall incidence of non-canonical IDH1 mutations was 7.9% (95% CI 5.4-10.7%) in patients with IDH-mutated gliomas. There was no statistical difference in terms of incidence between patients with grade 2 or grade 3 glioma. Patients with non-canonical IDH mutations had a lower rate of 1p19q codeletion (risk difference 31%, 95% CI 23-38%) and presented a significantly prolonged survival (pooled HR 0.47, 95% CI 0.28-0.81) as compared to those with IDH1 R132H mutation.
CONCLUSION
Non-canonical IDH1 mutations occur in 7.9% of IDH-mutated gliomas and identify a specific subgroup of patients with an improved survival despite a lower rate of 1p19q codeletion. Data about the type of IDH mutation should be collected in clinical practice and within interventional trials as this could be a critical variable for improved stratification and selection of patients.
Topics: Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 34853984
DOI: 10.1007/s12325-021-01977-3 -
Annals of Oncology : Official Journal... Oct 2016Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%-20% of colorectal cancers... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%-20% of colorectal cancers (CRCs) harbor activating mutations in PIK3CA, making it one of the most frequently mutated genes in CRC. We thus carried out a systematic review and meta-analysis investigating the prognostic significance of PIK3CA mutations in CRC.
MATERIALS AND METHODS
Electronic databases were searched from inception through May 2015. We extracted the study characteristics and prognostic data of each eligible study. The hazard ratio (HR) and 95% confidence interval (CI) were derived and pooled using the random-effects Mantel-Haenszel model.
RESULTS
Twenty-eight studies enrolling 12 747 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 19 and 10 studies, respectively. Comparing PIK3CA-mutated CRC patients with PIK3CA-wild-type CRC patients, the summary HRs for OS and PFS were 0.96 (95% CI 0.83-1.12) and 1.20 (95% CI 0.98-1.46), respectively. The trim-and-fill, Copas model and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Five studies reported the CRC prognosis for PIK3CA mutations in exons 9 and 20 separately; neither exon 9 mutation nor exon 20 mutation in PIK3CA was significantly associated with patient survival.
CONCLUSIONS
Our findings suggest that PIK3CA mutation has the neutral prognostic effects on CRC OS and PFS. Evidence was accumulating for the establishment of CRC survival between PIK3CA mutations and patient-specific clinical or molecular profiles.
Topics: Biomarkers, Tumor; Class I Phosphatidylinositol 3-Kinases; Colorectal Neoplasms; Disease-Free Survival; Drug Resistance, Neoplasm; Humans; Mutation; Prognosis; Proportional Hazards Models
PubMed: 27436848
DOI: 10.1093/annonc/mdw264 -
JAMA Neurology Apr 2015In the past 2 years, 3 genes (SLC20A2, PDGFRB, and PDGFB) were identified as causative of primary familial brain calcification (PFBC), enabling genotype-specific... (Review)
Review
IMPORTANCE
In the past 2 years, 3 genes (SLC20A2, PDGFRB, and PDGFB) were identified as causative of primary familial brain calcification (PFBC), enabling genotype-specific phenotyping.
OBJECTIVES
To provide a systematic literature review on the neuroimaging and clinical phenotype of genetically confirmed PFBC and summarize known pathophysiological mechanisms, to improve and harmonize future phenotype description and reporting by addressing data gaps, and to develop uniform definitions for clinical characterization.
EVIDENCE REVIEW
We systematically searched the MEDLINE database among articles published from January 1, 2012, through May 31, 2014, for the 3 genes and selected 25 articles from all records (n=75) and from sources cited in the reference lists. Only genetically confirmed cases with individual clinical information were included, leaving 15 reports. Predefined categories for data extraction were different neurologic and psychiatric symptoms, imaging results, and age at onset (AAO). We also assessed availability of information to estimate possible bias.
FINDINGS
We included a total of 179 cases, 162 of which belong to 25 families. Availability of information ranged from 96.6% for ethnicity to 24.4% for AAO. All cases had calcifications on comprehensive cranial computed tomography, most frequently located in the basal ganglia (70.6%), subcortical white matter (40.8%), cerebellum (34.1%), or thalamus (28.5%). Mean (SD) AAO was 27.9 (22.3) years, and the AAO was comparable across genes (P=.77). The most frequently described signs were movement disorders, such as parkinsonism (12%) and dystonia (19%). Penetrance of the imaging phenotype was 100% compared with only 61% of the clinical phenotype. We propose a novel definition of disease status by specifying PFBC into genetic, clinical, and imaging phenotypes. Pathophysiological pathways converge on impaired phosphorus homeostasis and integrity of the blood-brain barrier.
CONCLUSIONS AND RELEVANCE
Especially in rare conditions, meta-analyses are the most suitable tool to extract reliable information on the natural course of a disease. For future analyses, we provide a minimal data set that can be used for systematic clinical and imaging data collection in PFBC and that will also improve informed counseling of patients.
Topics: Age of Onset; Brain Diseases; Calcinosis; Humans; Movement Disorders; Mutation; Phenotype
PubMed: 25686319
DOI: 10.1001/jamaneurol.2014.3889 -
Seizure Mar 2024To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence.
PURPOSE
To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence.
METHODS
Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy.
RESULTS
Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources.
SIGNIFICANCE
Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.
Topics: Humans; Epilepsy; Seizures; Genetic Testing; Mutation; Databases, Factual; Phenotype
PubMed: 37777370
DOI: 10.1016/j.seizure.2023.09.021 -
PloS One 2018Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of this study were to assess the heterogeneity, estimate pooled proportions and describe the preponderance of FQ-resistance determinants in typhoidal and non-typhoidal Salmonella (NTS) isolates of Africa.
METHODS
Genetic and phenotypic data on 6103 Salmonella isolates were considered. Meta- and frequency analyses were performed depending on the number of studies by category, number of isolates and risks of bias. A random effects model was used to assess heterogeneity and estimate pooled proportions. Relative and cumulative frequencies were calculated to describe the overall preponderance of FQ-resistance determinants in quinolone resistant isolates.
RESULTS
The pooled proportion of gyrA mutants (Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis) was estimated at 5.7% (95% Confidence interval (CI) = 2.6, 9.8; Tau squared (T2) = 0.1105), and was higher in S. Typhi than in S. Typhimurium (odds ratio (OR) = 3.3, 95%CI = 2, 5.7). The proportions of each of gyrB and parC mutants, and strains with Plasmid Mediated Quinolone Resistance genes (qnrA, qnrB and qnrS) were low (≤ 0.3%). Overall, 23 mutant serotypes were identified, and most strains had mutations at codons encoding Ser83 and Asp87 of gyrA (82%, 95%CI = 78, 86).
CONCLUSIONS
Mutations at gyrA appear to account for ciprofloxacin non-susceptibility in most clinical Salmonella strains in Africa. The estimates could be harnessed to develop a mismatch-amplification mutation-assay for the detection of FQ-resistant strains in Africa.
Topics: Africa; Drug Resistance, Bacterial; Fluoroquinolones; Molecular Epidemiology; Mutation; Salmonella
PubMed: 29432492
DOI: 10.1371/journal.pone.0192575 -
Oral Oncology May 2023To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role.
MATERIALS AND METHODS
The databases Medline (via Ovid), Embase (via Ovid), Cochrane Library, Scopus, and Web of Science (Core Collection) were searched from inception to December 2022 to identify studies analysing TERT promoter mutations in HNSCC. Pooled prevalence of TERT promoter mutations and hazard ratio (sHR) of death/progression, with corresponding confidence intervals (CI), were estimated.
RESULTS
The initial search returned 6416 articles, of which 17 studies, including 1830 patients, met the criteria for prevalence meta-analysis. Among them, 8 studies fitted the inclusion criterion to analyse the prognostic impact of TERT promoter mutations. Overall, 21% (95% CI: 12%-31%) of HNSCCs harboured TERT promoter mutation. TERT promoter mutations were more commonly found in oral cavity cancer (prevalence = 47%, 95% CI: 33%-61%), followed by laryngeal/hypopharyngeal cancer (prevalence = 12%, 95% CI: 4%-25%), while they were quite rare in oropharyngeal cancer (prevalence = 1%, 95% CI: 0%-4%). TERT promoter mutation -124 C > T was associated with a higher risk of death (sHR = 2.01, 95% CI: 1.25-3.23) and progression (sHR = 2.79, 95% CI: 1.77-4.40), while -146 C > T TERT promoter mutation did not show any significant correlation neither to overall nor progression-free survival.
CONCLUSION
TERT promoter mutations were mainly topographically restricted to oral cavity cancer. -124 C > T was the most common TERT promoter mutation and was significantly associated to worse outcome in HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Prevalence; Mouth Neoplasms; Laryngeal Neoplasms; Telomerase; Head and Neck Neoplasms; Mutation
PubMed: 37075587
DOI: 10.1016/j.oraloncology.2023.106398 -
The Libyan Journal of Medicine Jun 2013Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 gene mutations and characterized by permanent neonatal diabetes (PNDM), skeletal dysplasia, and recurrent... (Review)
Review
BACKGROUND
Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 gene mutations and characterized by permanent neonatal diabetes (PNDM), skeletal dysplasia, and recurrent hepatitis. The frequency of this rare syndrome is largely unknown.
OBJECTIVES
To define the frequency and spectrum of WRS in the Kingdom of Saudi Arabia (KSA) based on published data.
METHODS
The Medline database was searched for published articles on WRS. The number of reported cases from KSA was compared to the total number of WRS cases reported worldwide. The genotype and phenotype of WRS patients from KSA were reviewed.
RESULTS
Ten articles describing 23 WRS patients from 12 Saudi families from 1995 to 2012 were identified. This figure accounts for 27.7% (23/83) of the patients and 22.2% (12/54) of the families with WRS reported worldwide until January 2013. All Saudi patients with WRS presented with PNDM, and they represent 59% of all PNDM cases from WRS. At reporting, 73% of patients experienced recurrent hepatitis, 56.5% had skeletal abnormalities, and 39.1% of them were dead. There was a variation in the phenotype even between affected siblings. Genetic diagnosis was confirmed in all 12 families with no correlation between the genotype and phenotype. Eight of the nine EIF2AK3 mutations were only reported in these families, and one was shared with a patient from Qatar, a neighboring Arab state.
CONCLUSIONS
No study on the frequency of WRS has been published. However, the available data indicate that KSA has the largest collection of patients with WRS worldwide, and nine of the identifiable EIF2AK3 mutations appear to be confined to Arabs. Establishing a national or international registry for WRS would provide more reliable data on this rare condition.
Topics: Age of Onset; Child; Child, Preschool; Diabetes Mellitus, Type 1; Epiphyses; Female; Genotype; Humans; Infant; Infant, Newborn; Male; Mutation; Osteochondrodysplasias; Phenotype; Prognosis; Saudi Arabia; eIF-2 Kinase
PubMed: 23759358
DOI: 10.3402/ljm.v8i0.21137 -
Clinical and Experimental Dermatology Jan 2010This review summarizes clinically important findings from nine systematic reviews indexed in bibliographical databases between August 2007 and August 2008, dealing with... (Review)
Review
This review summarizes clinically important findings from nine systematic reviews indexed in bibliographical databases between August 2007 and August 2008, dealing with the definitions, causes and consequences of atopic eczema (AE). One review of diagnostic criteria found that out of 10 sets of criteria, only the UK refinement of the Hanifin and Rajka criteria have been adequately tested (in 19 studies). Another review of 20 named outcome measures found that only three [SCORing Atopic Dermatitis (SCORAD), the Eczema Area and Severity Index (EASI) and the Patient Oriented Eczema Measure (POEM)] had been tested and found to perform adequately. In terms of risk factors for developing disease, a review found that birth by caesarean section increased the risk of asthma and hay fever but not eczema in offspring. A review of cohort studies also found evidence that adverse psychological factors in early life predispose to more atopic disease and a worse prognosis. Another review found that filaggrin gene mutations were a consistently strong risk factor for AE, with a person carrying one of these mutations being over three times more likely to exhibit eczema. It has been suggested that eczema might protect against some forms of cancer, and a detailed systematic review of brain cancers that included 53,233 participants from eight case-control and cohort studies found that having atopic disease was associated with a 39% reduction in glioma risk, a finding that was also present for just those with AE (odds ratio 0.69, 95% CI 0.58-0.82). A further review of case-control and cohort studies failed to find any association between keeping furry pets at birth and subsequent risk of eczema, although pet fur might still exacerbate established disease. In terms of disease consequences, a review found that eczema was the commonest cause of chronic sleep loss in young people, affected the whole family. A review of four economic studies from the US found that the annual cost of AE in the States was as high as $3.8 billion when indirect costs are included.
Topics: Clinical Trials as Topic; Dermatitis, Atopic; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Mutation; Prognosis; Risk Factors
PubMed: 19874343
DOI: 10.1111/j.1365-2230.2009.03733.x -
Journal of Pediatric Endocrinology &... Jun 2022Differentiated thyroid cancers (DTCs) in the paediatric population differ from that of their adult counterparts in terms of clinicopathological characteristics and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Differentiated thyroid cancers (DTCs) in the paediatric population differ from that of their adult counterparts in terms of clinicopathological characteristics and treatment outcomes. This systematic review and meta-analysis was conducted to comprehensively evaluate the prevalence of various genetic alterations underlying the pathogenesis of sporadic paediatric DTCs.
METHODS
This study followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Systematic searches were made on the PubMed and Embase databases using relevant keywords, and articles published until October 15, 2021 were selected. Data on the prevalence of various genetic alterations were extracted from the individual articles. Random-effects model was employed for meta-analysis to generate pooled estimates and their 95% confidence intervals (95% CIs).
RESULTS
Thirty-three articles comprising 1,380 paediatric patients were included. rearrangement (pooled prevalence: 24.4%, 95% CI: 19.1-30.1) was observed to be the most common genetic alteration in sporadic paediatric DTCs, closely followed by point mutation (pooled prevalence: 21.2%, 95% CI: 17.2-25.5). Other common alterations included: rearrangement (pooled prevalence: 13.5%, 95% CI: 9.5-17.9) and mutation (pooled prevalence: 12.5%, 95% CI: 3.6-25.7). and mutations were observed to be relatively uncommon (pooled prevalence: 5.7%, 95% CI: 2.9-9.3, and 2.2%, 95% CI: 0.4-5.5, respectively). There was no evidence of publication bias.
CONCLUSIONS
Fusion oncogenes are noted to be the major oncogenic drivers in sporadic paediatric DTCs and underlie their unique behaviour. However, despite the relatively lower frequency of point mutation compared to adults, it remains a major player in childhood DTCs.
Topics: Adult; Child; DEAD-box RNA Helicases; Genomics; Humans; Mutation; Point Mutation; Proto-Oncogene Proteins B-raf; Ribonuclease III; Thyroid Neoplasms
PubMed: 35434981
DOI: 10.1515/jpem-2021-0741 -
Journal of Clinical Neuroscience :... Sep 2016Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between... (Meta-Analysis)
Meta-Analysis Review
Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma-related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p=0.043 for the WHO grade II gliomas, p=0.002 for the grade III gliomas and p=0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Epilepsy; Female; Glioma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Young Adult
PubMed: 27406953
DOI: 10.1016/j.jocn.2015.11.030