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African Journal of Paediatric Surgery :... 2015This was a meta-analysis and systematic review to determine the global prevalence of the mitochondrially encoded 12S RNA (MT-RNR1) genetic mutation in order to assess... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis and systematic review of the prevalence of mitochondrially encoded 12S RNA in the general population: Is there a role for screening neonates requiring aminoglycosides?
BACKGROUND
This was a meta-analysis and systematic review to determine the global prevalence of the mitochondrially encoded 12S RNA (MT-RNR1) genetic mutation in order to assess the need for neonatal screening prior to aminoglycoside therapy.
MATERIALS AND METHODS
A comprehensive search of MEDLINE, EMBASE, Ovid, Database of Abstracts of Reviews of Effect, Cochrane Library, Clinical Evidence and Cochrane Central Register of Trials was performed including cross-referencing independently by 2 assessors. Selections were restricted to human studies in English. Meta-analysis was done with MetaXL 2013.
RESULTS
Forty-five papers out of 295 met the criteria. Pooled prevalence in the general population for MT-RNR1 gene mutations (A1555G, C1494T, A7445G) was 2% (1-4%) at 99%.
CONCLUSION
Routine screening for MT-RNR1 mutations in the general population prior to treatment with aminoglycosides appear desirable but poorly supported by the weak level of evidence available in the literature. Routine screening in high-risk (Chinese and Spanish) populations appear justified.
Topics: Aminoglycosides; Genetic Testing; Humans; Infant, Newborn; Mitochondria; Mutation; Prevalence; RNA, Ribosomal
PubMed: 26168747
DOI: 10.4103/0189-6725.160342 -
Critical Reviews in Oncology/hematology Nov 2021Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common mutations with tumour budding.
METHODS
A systematic review of studies relating to tumour budding and genetic mutation in CRC was performed. The relationship between mutational status and tumour budding was evaluated using meta-analysis.
RESULTS
A total of 6153 patients from 17 articles were included. According to the meta-analysis, high-grade tumour budding was significantly associated with KRAS mutation (OR = 1.52, 95 %CI: 1.13-2.02, P = 0.005) and MSS/pMMR (OR = 2.06, 95 %CI: 1.42-2.97, P = 0.0001).
CONCLUSION
The significant association between high-grade tumour budding and mutated KRAS or MSS/pMMR may suggest a role of these mutations in the development of the tumour budding phenotype and be useful for stratifying patient outcome in CRC.
Topics: Colorectal Neoplasms; Humans; Mutation; Phenotype; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 34619332
DOI: 10.1016/j.critrevonc.2021.103490 -
Journal of Orofacial Orthopedics =... Jul 2013The goal of this work was to identify all known gene mutations that have been associated with the development of nonsyndromic oligodontia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The goal of this work was to identify all known gene mutations that have been associated with the development of nonsyndromic oligodontia.
METHODS
A systematic literature search was performed electronically in two databases (PubMed, Medpilot) supplemented by a hand search. Articles published up to March 2012 were considered. Search terms were combined as follows: oligodontia and genes, oligodontia and mutations, tooth agenesis and genes, and tooth agenesis and mutations. A meta-analysis of the data was conducted based on the Tooth Agenesis Code (TAC).
RESULTS
Seven genes are currently known to have a potential for causing nonsyndromic oligodontia. All these genes vary both in terms of number of identified mutations and in terms of number of documented patients: 33 mutations and 93 patients are on record for PAX9, 10 mutations and 51 patients for EDA, 12 mutations and 33 patients for MSX1, 6 mutations and 17 patients for AXIN2, and 1 mutation in 1 patient for EDARADD, NEMO, and KRT17 each. A total TAC score of 250 was found to have cutoff properties, as 100% of MSX1 and 80% of EDA patients exhibited TAC ≤ 250, whereas 96.9% of PAX9 and 90% of AXIN2 patients exhibited TAC >250. Furthermore, 94.3% of EDA patients but only 28.6% of MSX1 patients exhibited odd-numbered TAC scores in at least one quadrant, and 72.7% of PAX9 but none of the AXIN2 patients were found to show TAC scores of 112 in at least one quadrant.
CONCLUSION
In order of decreasing frequency, PAX9, EDA, MSX1, AXIN2, EDARADD, NEMO, and KRT17 are the seven genes currently known to have a potential for causing nonsyndromic oligodontia. TAC scores enabled us to identify an association between oligodontia phenotypes and genotypes in the patients covered by this meta-analysis.
Topics: Anodontia; Cytoskeletal Proteins; Genetic Predisposition to Disease; Humans; Mutation; Polymorphism, Single Nucleotide; Prevalence; Risk Assessment; Transcription Factors
PubMed: 23828301
DOI: 10.1007/s00056-013-0138-z -
Annals of Hematology Aug 2014Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are... (Meta-Analysis)
Meta-Analysis Review
Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis.
Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are used for risk classification in AML patients with normal karyotype (cytogenetically normal (CN)-AML). In this systematic review and meta-analysis, we examined three frequent mutations in CN-AML: mutations of fms-related tyrosine kinase 3 (FLT3-ITD), mutated nucleophosmin (NPM1), and mutations of the CCAAT enhancer-binding protein alpha (CEBPA) gene. A systematic literature search of publications listed in the electronic databases (Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge and Cochrane) from 2000 up to March 2012 was performed (Fig. 1). Nineteen studies were included and qualitatively analyzed. Two to four studies entered the quantitative meta-analysis incorporating 1,378 to 1,942 patients with CN-AML. Meta-analysis for overall survival (OS) and relapse-free survival (RFS) showed FLT3-ITD to predict an unfavorable prognosis, with hazard ratios (HR) of 1.86 and 1.75, respectively. In contrast, meta-analysis of the impact of NPM1 and CEBPA mutations on OS yielded an HR of 0.56 for each mutation, while analysis of impact on RFS produced HRs of 0.37 and 0.42, respectively. This systematic review and meta-analysis aimed to evaluate the prognostic value of mutations in the NPM1, CEBPA, and FLT3 genes. FLT3-ITD was associated with worse prognosis, whereas mutations in NPM1 and CEBPA genes were associated with a favorable prognosis.
Topics: Adult; Age Factors; CCAAT-Enhancer-Binding Proteins; Clinical Trials as Topic; Disease-Free Survival; Female; Humans; Karyotype; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nuclear Proteins; Nucleophosmin; Proportional Hazards Models; Survival Analysis; Tandem Repeat Sequences; Treatment Outcome; Young Adult; fms-Like Tyrosine Kinase 3
PubMed: 24801015
DOI: 10.1007/s00277-014-2072-6 -
Journal of Pediatric Hematology/oncology Jul 2017It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted... (Meta-Analysis)
Meta-Analysis Review
It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted based on rare cases. We systematically searched bibliographic databases, including PubMed, Embase, and COSMIC for articles which are related to diseases covered by DICER1 syndrome. The weighted summary of mutation frequencies among patients with pleuropulmonary blastoma (PPB), cystic nephroma (CN), and Sertoli-Leydig cell tumor (SLCT) were calculated. Forty-nine eligible articles were included. In total, 72 cases with multimorbidity of DICER1 syndrome were identified. More females (n=46, 64%) presented with multimorbidity than males (n=18, 25%) and the remaining 8 patients' sex were unknown. Nineteen of 72 patients with multimorbidity suffered from another disease that was not yet included in DICER1 syndrome, which would provide potential phenotypes of DICER1 syndrome. The germline DICER1 mutation frequencies in PPB, CN, and SLCT were 66.9%, 73.2%, and 57.1%, respectively. The somatic DICER1 mutation frequencies of PPB, CN, and SLCT were 92.4%, 87.9%, and 43.3%, respectively. Majority of patients with multimorbidity of DICER1 syndrome were mutation positive individuals so that multimorbidity may suggest the possible germline mutation of these patients and their relatives.
Topics: DEAD-box RNA Helicases; Female; Germ-Line Mutation; Humans; Male; Mutation Rate; Nephroma, Mesoblastic; Pulmonary Blastoma; Ribonuclease III; Sertoli-Leydig Cell Tumor
PubMed: 27906793
DOI: 10.1097/MPH.0000000000000715 -
Biochimica Et Biophysica Acta. Reviews... Dec 2019Breast cancer has, due to its high incidence, the highest mortality of cancer in women. The most common molecular type of breast cancer is the luminal subtype, which... (Meta-Analysis)
Meta-Analysis Review
The association between type of endocrine therapy and development of estrogen receptor-1 mutation(s) in patients with hormone-sensitive advanced breast cancer: A systematic review and meta-analysis of randomized and non-randomized trials.
BACKGROUND
Breast cancer has, due to its high incidence, the highest mortality of cancer in women. The most common molecular type of breast cancer is the luminal subtype, which expresses estrogen and progesterone receptors and is typically treated with surgery and adjuvant endocrine therapy (ET). Estrogen receptor alpha (ERα), encoded by the estrogen receptor-1 (ESR1) gene, is expressed in approximately 70% of all breast cancers, and ET represents a major treatment modality in ERα-positive cancers. However, resistance to different ET evolves frequently, leading to disease progression or recurrence in ER+ breast cancer. Acquired mutations in the Ligand Binding Domain (LBD) of the ERα referred as ESR1 mutations; could be selected by ET itself leading to resistance over the course of ET therapy.
OBJECTIVE
The goal of this review is to estimate the effect of Aromatase Inhibitors (AIs), Tamoxifen (TAM) and Fulvestrant (FUL) on the development of ESR1 mutations in hormone-sensitive advanced breast cancer.
METHODS
A systematic review of qualitative studies published between January 1st, 2007 and March 1st, 2019 was conducted using the PubMed and Thomas Reuters Web of Science databases. Search terms included ESR1 mutations, estrogen receptor, breast cancer, recurrent, metastatic disease, aromatase inhibitors, fulvestrant and tamoxifen. Only full-text studies in English concerning the development of ESR1 mutations and their outcomes on disease progression were included. Selection of studies was performed using predefined data fields, taking study quality indicators into consideration. Inclusion criteria of the study populations were: Ghoncheh et al. (2016) [1] female patients above 18 years; Nielsen et al. (2011) [2] Estrogen-receptor positive (ER+) breast cancer in the advanced setting; Reinert et al. (2017) [3] previous exposure to endocrine therapy including SERDs (preferably Fulvestrant), SERMs (preferably Tamoxifen) or Aromatase Inhibitors.
RESULTS
The current review enrolled 16 articles, including 4 multicentre double blinded RCTs and 12 cohorts and comprising a total of 2632 patients. The overall incidence rate of the ESR1 mutation was 24% (95% CI: 18%-31%). We observed that D538G was the most frequent ESR1 mutation. Several studies showed that prior endocrine therapy (AIs, TAM, FUL) could result in an ESR1 mutation and therapy resistance leading to disease progression or recurrence. Different mechanisms had been implied to explain the underlying ET resistance. One of the key findings of this work is the significant difference in ESR1 mutation incidence between patients with and without AI therapy (OR: 9.34, 95% CI: 3.28-26.62, P ≤.001).
CONCLUSION
ESR1 mutations are not uncommon phenomenon in patients with hormone-sensitive advanced breast cancer. There is a significant higher incidence rate of ESR1 mutations in patients with previous AI-containing therapeutic regimens, compared to those who received non-AI containing regimes. These ESR1 mutations could lead to the development of complete endocrine resistance to AI, whereas only partial resistance is seen in case of TAM or FUL.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Drug Resistance, Neoplasm; Estrogen Receptor alpha; Female; Fulvestrant; Humans; Mutation; Non-Randomized Controlled Trials as Topic; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 31647985
DOI: 10.1016/j.bbcan.2019.188315 -
Orphanet Journal of Rare Diseases Jul 2019Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis,... (Review)
Review
Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype-phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10, 1.69×10). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype-phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10, 3.93×10). The present review suggests that patients' ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.
Topics: Female; Humans; Male; alpha-Galactosidase; Cross-Sectional Studies; Genotype; Hemochromatosis; Mutation; Hemochromatosis Protein
PubMed: 31286966
DOI: 10.1186/s13023-019-1097-2 -
Human Mutation Jun 2007Despite the large body of mutational data available for melanoma and epidemiological studies linking this cancer to ultraviolet radiation (UVR), the fundamental... (Review)
Review
Despite the large body of mutational data available for melanoma and epidemiological studies linking this cancer to ultraviolet radiation (UVR), the fundamental carcinogenic mechanisms involved in melanoma remain largely unknown. To this end, we systematically reviewed, extracted, and analyzed mutational data from the extant melanoma literature in an effort to gain more insight into its early pathogenic events. We searched PubMed (1966-January 2006) using the words "mutation" AND "melanoma" in the title or abstract. Out of 2,095 returned results, there were 203 eligible studies that were subsequently analyzed. We cataloged 8,201 somatic and cultured melanoma specimens and annotated 2,041 reported somatic sequence variants. The single BRAF c.1799T>A (p.Val600Glu) alteration is the most prevalent variant while other A:T>T:A transversions were uncommon. Four highly-recurrent, non-ultraviolet B (UVB) changes account for most of the NRAS and BRAF variants. CDKN2A, PTEN/MMAC1, and TP53 harbored statistically higher rates of UVB signature changes (64.2%, 52.4%, and 69.2%, respectively) than oncogenic loci (NRAS: 15.3% and BRAF: 2.4%). More specifically, cutaneous melanomas showed a significantly higher proportion of UVB signature mutations at both TP53 and CDKN2A when compared to non-skin cancers using data from their respective locus-specific databases. Superficial spreading and nodular melanomas had the highest rates of BRAF (53.4%) and NRAS (28.0%) mutations. In melanoma, there is sufficient mutational evidence to support a role for direct UVB participation, especially at TP53 and CDKN2A. For oncogenes, the role for UVB is less clear since functionally-activating changes are uncommon and are subject to sequence constraints.
Topics: DNA Mutational Analysis; Genes, Tumor Suppressor; Humans; Melanoma; Mutation; Neoplasms, Radiation-Induced; Proto-Oncogenes; Skin Neoplasms; Ultraviolet Rays; Uveal Neoplasms
PubMed: 17295241
DOI: 10.1002/humu.20481 -
The Journal of Pediatrics Mar 2019To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated...
OBJECTIVES
To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations.
STUDY DESIGN
PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood. Clinical features, management, and genotype were extracted. Case notes of pediatric patients with erythromelalgia from the Great Ormond Street Hospital Pain Service were reviewed for clinical features, patient-reported outcomes, and treatments. Children aged over 10 years were recruited for quantitative sensory testing.
RESULTS
Twenty-eight publications described erythromelalgia associated with 15 different SCN9A gene variants in 25 children. Pain was severe and often refractory to multiple treatments, including nonspecific sodium channel blockers. Skin damage or other complications of cold immersion for symptomatic relief were common (60%). SCN9A mutations resulting in greater hyperpolarizing shifts in Na1.7 sodium channels correlated with symptom onset at younger ages (P = .016). Variability in reporting, and potential publication bias toward severe cases, limit any estimations of overall prevalence. In our case series, symptoms were similar but comorbidities were more common in children with SCN9A mutations. Quantitative sensory testing revealed marked dynamic warm allodynia.
CONCLUSIONS
Inherited erythromelalgia in children is associated with difficult-to-manage pain and significant morbidity. Standardized reporting of outcome and management in larger series will strengthen identification of genotype-phenotype relationships. More effective long-term therapies are a significant unmet clinical need.
Topics: Adolescent; Child; Erythromelalgia; Female; Humans; Male; Mutation; NAV1.7 Voltage-Gated Sodium Channel; Pain; Retrospective Studies; Symptom Assessment
PubMed: 30416015
DOI: 10.1016/j.jpeds.2018.10.024 -
Journal of Translational Medicine Feb 2024Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head and neck squamous cell carcinoma (HNSCC) has not yet been specifically addressed. Since HNSCC patients exhibit a rather limited response to ICIs, there is an unmet need to develop predictive biomarkers to improve patient selection criteria and the clinical benefit of ICI treatment.
METHODS
We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. HNSCC cohort studies were selected when TMB prior to ICI treatment was evaluated, TMB cutoff value was available, and the prognostic value of TMB was evaluated by time-to-event survival analysis. A total of 11 out of 1960 articles were analyzed, including 1200 HNSCC patients.
RESULTS
The results showed that those patients harboring high TMB exhibited a significantly superior overall response rate (OR = 2.62; 95% CI 1.74-3.94; p < 0.0001) and a survival advantage (HR = 0.53; 95% CI 0.39-0.71; p < 0.0001) after ICI treatment.
CONCLUSION
This is the first meta-analysis to demonstrate a higher response and clinical benefit from ICI therapy in HNSCC patients with high TMB.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Immunotherapy; Survival Analysis; Biomarkers, Tumor; Head and Neck Neoplasms; Mutation
PubMed: 38311741
DOI: 10.1186/s12967-024-04937-x