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Mutation Research. Reviews in Mutation... 2024Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are... (Comparative Study)
Comparative Study Review
Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was TP53, followed by PIK3CA, CDKN2A, NOTCH1 and FAT1. Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.
Topics: Humans; Circulating Tumor DNA; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mutation; Class I Phosphatidylinositol 3-Kinases; Biomarkers, Tumor; Tumor Suppressor Protein p53; Receptor, Notch1; DNA, Neoplasm; Cyclin-Dependent Kinase Inhibitor p16; Cadherins
PubMed: 37977279
DOI: 10.1016/j.mrrev.2023.108477 -
Scientific Reports Nov 2015Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene.... (Meta-Analysis)
Meta-Analysis Review
Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese), and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: "familial hypercholesterolemia", "Chinese", "China", "Hong Kong", and "Taiwan". A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y, and A606T, and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database.
Topics: China; Computer Simulation; Databases, Genetic; Hong Kong; Humans; Hyperlipoproteinemia Type II; Lipids; Mutation; Mutation Rate; Phenotype; Receptors, LDL; Taiwan
PubMed: 26608663
DOI: 10.1038/srep17272 -
The CHEK2 I157T variant and colorectal cancer susceptibility: a systematic review and meta-analysis.Asian Pacific Journal of Cancer... 2012The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of colorectal cancer, but it is unclear whether the evidence is... (Review)
Review
BACKGROUND
The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of colorectal cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice.
MATERIALS AND METHODS
We systematically searched PubMed, EMBASES, Elsevier and Springer for relevant articles before Apr 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effects or random-effects models with Review Manager 5.0 software.
RESULTS
A total of seven studies including 4,029 cases and 13,844 controls based on the search criteria were included for analysis. A significant association of the CHEK2 I157T C variant with unselected CRC was found (OR=1.61, 95% CI=1.40-1.87, P<0.001). We also found a significant association with sporadic CRC (OR=1.48, 95% CI=1.23-1.77, P<0.001) and separately with familial CRC (OR=1.97, 95% CI=1.41-2.74, P<0.001).
CONCLUSION
This meta-analysis demonstrates that the CHEK2 I157T variant may be another important CRC-predisposing gene, which increases CRC risk, especially in familial CRC.
Topics: Checkpoint Kinase 2; Colorectal Neoplasms; Genetic Predisposition to Disease; Humans; Meta-Analysis as Topic; Mutation; Prognosis; Protein Serine-Threonine Kinases; Review Literature as Topic; Risk Factors
PubMed: 22901170
DOI: 10.7314/apjcp.2012.13.5.2051 -
Neurological Sciences : Official... Mar 2023Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in > 80 loci designated SPG (SPastic parapleGia). The phenotypic spectrum of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in > 80 loci designated SPG (SPastic parapleGia). The phenotypic spectrum of HSP can extend to include other neurologic features, including movement disorders. Our aim was to investigate genotype-phenotype associations in HSP with a focus on movement disorders.
METHODS
We performed a systematic review and individual participant data (IPD)-level meta-analysis by retrieving publications from Medline/EMBASE/Web of Science on HSP with a SPG genotype. Studies were included only if individual-level information was accessible and at least one patient with a movement disorder was reported for that genotype. Out of 21,957 hits, 192 manuscripts with a total of 1413 HSP cases were eligible. Data were compared between two HSP groups: manifested with (HSP-MD, n = 767) or without (HSP-nMD, n = 646) a movement disorder.
RESULTS
The HSP-MD group had an older age of onset (20.5 ± 16.0 vs. 17.1 ± 14.2 yr, p < 0.001) and less frequent autosomal dominant inheritance (7.6% vs. 30.1%, p < 0.001) compared to HSP-nMD. SPG7 (31.2%) and SPG11 (23.8%) were the most frequent genotypes in the HSP-MD group. HSP-MD with SPG7 had higher frequency of later onset during adulthood (82.9% vs. 8.5%), ataxia (OR = 12.6), extraocular movement disturbances (OR = 3.4) and seizure (OR = 3.7) compared to HSP-MD with SPG11. Conversely, SPG11 mutations were more frequently associated with consanguinity (OR = 4.1), parkinsonism (OR = 7.8), dystonia (OR = 5.4), peripheral neuropathy (OR = 26.9), and cognitive dysfunction (OR = 34.5).
CONCLUSION
This systematic IPD-level meta-analysis provides the largest data on genotype-phenotype associations in HSP-MD. Several clinically relevant phenotypic differences were found between various genotypes, which can possibly facilitate diagnosis in resource-limited settings.
Topics: Humans; Spastic Paraplegia, Hereditary; Paraplegia; Mutation; Movement Disorders; Phenotype; Proteins
PubMed: 36441344
DOI: 10.1007/s10072-022-06516-8 -
Journal of Neurodevelopmental Disorders Jan 2022Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively... (Meta-Analysis)
Meta-Analysis Review
Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics.
BACKGROUND
Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN.
METHOD
A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis.
RESULTS
Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common).
CONCLUSIONS
Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics.
Topics: Autism Spectrum Disorder; Germ-Line Mutation; Humans; Mutation; PTEN Phosphohydrolase; Prevalence; Retrospective Studies
PubMed: 34983360
DOI: 10.1186/s11689-021-09406-w -
International Journal of Environmental... Jul 2021Over the last decades, the incidence of melanoma has been steadily growing, with 4.2% of the population worldwide affected by cutaneous melanoma (CM) in 2020 and with a... (Review)
Review
BACKGROUND AND AIM
Over the last decades, the incidence of melanoma has been steadily growing, with 4.2% of the population worldwide affected by cutaneous melanoma (CM) in 2020 and with a higher incidence and mortality in men than in women. We investigated both the risk factors for CM development and the prognostic and predictive factors for survival, stratifying for both sex and gender.
METHODS
We conducted a systematic review of studies indexed in PUB-MED, EMBASE, and Scopus until 4 February 2021. We included reviews, meta-analyses, and pooled analyses investigating differences between women and men in CM risk factors and in prognostic and predictive factors for CM survival.
DATA SYNTHESIS
Twenty-four studies were included, and relevant data extracted. Of these, 13 studies concerned potential risk factors, six concerned predictive factors, and five addressed prognostic factors of melanoma.
DISCUSSION
The systematic review revealed no significant differences in genetic predisposition to CM between males and females, while there appear to be several gender disparities regarding CM risk factors, partly attributable to different lifestyles and behavioral habits between men and women. There is currently no clear evidence of whether the mutational landscapes of CM differ by sex/gender. Prognosis is justified by a complex combination of phenotypes and immune functions, while reported differences between genders in predicting the effectiveness of new treatments are inconsistent. Overall, the results emerging from the literature reveal the importance of considering the sex/gender variable in all studies and pave the way for including it towards precision medicine.
CONCLUSIONS
Men and women differ genetically, biologically, and by social construct. Our systematic review shows that, although fundamental, the variable sex/gender is not among the ones collected and analyzed.
Topics: Female; Humans; Male; Melanoma; Mutation; Prognosis; Risk Factors; Sex Factors; Skin Neoplasms
PubMed: 34360236
DOI: 10.3390/ijerph18157945 -
BMJ (Clinical Research Ed.) Jul 2009To investigate whether filaggrin gene defects, present in up to one in 10 western Europeans and North Americans, increase the risk of developing allergic sensitisation... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate whether filaggrin gene defects, present in up to one in 10 western Europeans and North Americans, increase the risk of developing allergic sensitisation and allergic disorders.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, ISI Science Citation Index, BIOSIS, ISI Web of Knowledge, UK National Research Register, clinical trials.gov, the Index to Theses and Digital dissertations, and grey literature using OpenSIGLE.
STUDY SELECTION
Genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergic sensitisation or allergic disorders.
DATA EXTRACTION
Atopic eczema or dermatitis, food allergy, asthma, allergic rhinitis, and anaphylaxis, along with relevant immunological variables relating to the risk of allergic sensitisation as assessed by either positive skin prick testing or increased levels of allergen specific IgE.
DATA SYNTHESIS
24 studies were included. The odds of developing allergic sensitisation was 1.91 (95% confidence interval 1.44 to 2.54) in the family studies and 1.57 (1.20 to 2.07) in the case-control studies. The odds of developing atopic eczema was 1.99 (1.72 to 2.31) in the family studies and 4.78 (3.31 to 6.92) in the case-control studies. Three studies investigated the association between filaggrin gene mutations and allergic rhinitis in people without atopic eczema: overall odds ratio 1.78 (1.16 to 2.73). The four studies that investigated the association between filaggrin gene mutations and allergic rhinitis in people with atopic eczema reported a significant association: pooled odds ratio from case-control studies 2.84 (2.08 to 3.88). An overall odds ratio for the association between filaggrin gene mutations and asthma in people with atopic eczema was 2.79 (1.77 to 4.41) in case-control studies and 2.30 (1.66 to 3.18) in family studies. None of the studies that investigated filaggrin gene mutations and asthma in people without atopic eczema reported a significant association; overall odds ratio was 1.30 (0.7 to 2.30) in the case-control studies. The funnel plots suggested that publication bias was unlikely to be an explanation for these findings. No studies investigated the association between filaggrin gene mutations and food allergy or anaphylaxis.
CONCLUSIONS
Filaggrin gene defects increase the risk of developing allergic sensitisation, atopic eczema, and allergic rhinitis. Evidence of the relation between filaggrin gene mutations and atopic eczema was strong, with people manifesting increased severity and persistence of disease. Filaggrin gene mutations also increased the risk of asthma in people with atopic eczema. Restoring skin barrier function in filaggrin deficient people in early life may help prevent the development of sensitisation and halt the development and progression of allergic disease.
Topics: Epidemiologic Methods; Filaggrin Proteins; Humans; Hypersensitivity; Intermediate Filament Proteins; Mutation; Pedigree; Risk Factors
PubMed: 19589816
DOI: 10.1136/bmj.b2433 -
Journal of Clinical Immunology Jan 2023Sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD) syndrome is a novel rare autoinflammatory multisystem disorder. We... (Review)
Review
BACKGROUND AND PURPOSE
Sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD) syndrome is a novel rare autoinflammatory multisystem disorder. We performed a systematic review of the available clinical and therapeutics aspects of the SIFD syndrome.
METHODS
A systematic review according to PRISMA approach, including all articles published before the 30 of July 2021 in Pubmed and EMBASE database, was performed.
RESULTS
The search identified 29 publications describing 58 unique patients. To date, 41 unique mutations have been reported. Onset of disease is very early with a median age of 4 months (range 0-252 months). The most frequent manifestations are haematologic such as microcytic anaemia or sideroblastic anaemia (55/58), recurrent fever (52/58), neurologic abnormalities (48/58), immunologic abnormalities in particular a humoral immunodeficiency (48/58), gastrointestinal signs and symptoms (38/58), eye diseases as cataract and retinitis pigmentosa (27/58), failure to thrive (26/58), mucocutaneous involvement (29/58), sensorineural deafness (19/58) and others. To date, 19 patients (35.85%) died because of disease course (16) and complications of hematopoietic cell stems transplantation (3). The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) is dramatically changing the natural history of this disease.
CONCLUSIONS
SIFD syndrome is a novel entity to consider in a child presenting with recurrent fever, anaemia, B-cell immunodeficiency and neurodevelopmental delay. To date, therapeutic guidelines are lacking but anti-TNFα treatment and/or HCST are attractive and might modify the clinical course of this syndrome.
Topics: Child; Humans; Anemia, Sideroblastic; Immunologic Deficiency Syndromes; Fever; Mutation; Developmental Disabilities
PubMed: 35984545
DOI: 10.1007/s10875-022-01343-0 -
PloS One 2015The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to... (Review)
Review
Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.
BACKGROUND
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
METHODS
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
RESULTS
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
CONCLUSIONS
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
Topics: Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Meta-Analysis as Topic; Mutation; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 25816236
DOI: 10.1371/journal.pone.0120470 -
Medicinal Research Reviews Nov 2015GATA3 is a critical transcription factor in the development of various human systems. The notion that GATA3 expression is required for the differentiation and... (Review)
Review
GATA3 is a critical transcription factor in the development of various human systems. The notion that GATA3 expression is required for the differentiation and maintenance of normal breast tissue has been well established. Recently, GATA3 is found to actively participate in the multistep process leading breast cancer pathogenesis, including tumorigenesis, tumor differentiation, epithelial mesenchymal transition, and metastasis through regulation of various target genes. On the other hand, several studies have raised questions and highlighted the role of GATA3-low or GATA3-negative cells during the malignant development of breast cancer. In addition to gene expression, GATA3 mutations provide another dimension of complexity. As one of the most frequently mutated genes in breast cancer, GATA3 mutations may have an effect on DNA-binding ability, protein production, and transactivation activity. Recognition of the multiple function of GATA3 in breast cancer will serve to deepen our understanding of the nature of this disease and develop novel therapeutic approaches.
Topics: Breast Neoplasms; Female; GATA3 Transcription Factor; Humans; Mutation
PubMed: 26313026
DOI: 10.1002/med.21362