It was not possible to detect BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma: A diagnostic accuracy study.

BACKGROUND: The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma. METHODS: This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated. RESULTS: Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%. CONCLUSION: Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.

BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis.

BACKGROUND: Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas. METHODS: This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%. RESULTS: Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24-73.89), favoring radical treatment. CONCLUSION: BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.

Is oral microbiota associated with overweight and obesity in children and adolescents? A systematic review.

This article aims to verify the relationship between the composition and diversity of oral microbiota with overweight and obese children and adolescents. This systematic review was registered in PROSPERO, followed PRISMA 2020, and included an electronic search until March 2022, in PubMed/MEDLINE, Web of Science, Scopus, and The Cochrane Library databases. Studies were eligible if they compared the oral microbiota according to nutrition status among children and adolescents. Independent peers using JBI Critical Appraisal Checklists assessed the quality of studies. Eleven studies were eligible to be included in this review, with a total of 1,695 children and adolescents, 224 were obese, 190 were overweight, 1,154 were eutrophics and 127 were underweight. The most frequent phyla in overweight and obese children and adolescents, in comparison to their counterparts were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria. It was identified that nine of the eleven articles selected showed an association between oral microbiota and overweight and obesity in children and adolescents. We observed that there is an important association between oral bacterial composition diversity and overweight and obesity. This finding indicates the relevance of the evaluation and surveillance in oral health to control cases of overweight and obesity in children and adolescents.

Polymorphisms on rs9939609 FTO and rs17782313 MC4R genes in children and adolescent obesity: A systematic review.

The aim of this review was to assess whether the presence of rs9939609 and rs17782313 polymorphisms increase the risk for obesity among children and adolescents. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and it was registered in PROSPERO. The search was performed in the PubMed/Medline, The Cochrane Library, and Web of Science databases. The risk of bias of the studies was accessed using the Newcastle-Ottawa scale and JBI Critical Appraisal Checklist for Analytical. The search of the databases retrieved 859 references. Twelve studies were eligible to be included in this systematic review. Five studies founded a positive association between overweight and obesity in children and adolescents with the presence of the rs17783213 and four studies with rs9939609. Three studies did not find an association between overweight and obesity in children and adolescents with the presence of rs17782313 or rs9939609. One found a protective effect for obesity in individuals with risk A allele referring to rs9939609, one found a synergistic effect in relation to the presence of polymorphisms rs17782313 and rs9939609 for obese phenotype, and one observed that the presence together of the rs9939609, rs17782313, and rs12970134 MC4R were significant for the presence of obesity in children and adolescents. The results suggest that depending on the population evaluated and ethnicity, the polymorphisms rs17782313 and rs9939609 could be associated with overweight and obesity in children and adolescents.

MBL2 gene polymorphisms in HHV-8 infection in people living with HIV/AIDS.

BACKGROUND: Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients. RESULTS: A cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard® Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI = 1.2-7.6) of their last CD4 cell count being below 350 cells/mm3. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO. CONCLUSIONS: Host genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.

Influence of a TNF-α Polymorphism on the Severity of Schistosomiasis Periportal Fibrosis in the Northeast of Brazil.

AIMS: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is an essential component in the host immune response to infection, and it has been reported to be an important mediator in severe periportal fibrosis (PPF). We hypothesized that the (-G308A) polymorphism of the TNF-α gene is associated with the severity of PPF and that these polymorphisms influence TNF-α expression. METHODS: In this cross-sectional study, we genotyped these polymorphisms within the TNF-α gene in 256 Brazilian subjects infected with Schistosoma mansoni, with different patterns of PPF. RESULTS: The genotype (-308) AA was associated with a significant increase in the risk to advanced PPF (OR = 4.60; p = 0.009). In addition, median levels of TNF-α were higher in patients with moderate to advanced PPF, compared with mild fibrosis (20 and 17.3 pg/mL, respectively; p = 0.040). There was no association between average serum levels of TNF-α and (-G308A) TNF-α polymorphism. CONCLUSIONS: Our results suggest the (-308) AA genotype may be a risk factor for severity in advanced PPF, in this Brazilian population, and could potentially be used to predict the severity of advanced PPF in schistosomiasis.

Association Between Polymorphisms of the Mannose-Binding Lectin and Severity of Periportal Fibrosis in Schistosomiasis, in the Northeast of Brazil.

AIMS: Mannose-binding lectin (MBL) is a protein synthesized by the liver and its immune response is associated with the development of liver fibrosis. We hypothesized that the polymorphisms in the Exon 1 region (52, 54, 57) and promoter regions (-550 H/L, -221 X/Y) of the MBL2 gene were associated with the severity of periportal fibrosis (PPF), and that these polymorphisms affect the MBL serum levels. MATERIALS AND METHODS: In this cross-sectional study we genotyped these polymorphisms within the MBL2 gene in 229 Brazilian subjects infected with Schistosoma mansoni, with different patterns of PPF. RESULTS: There was no association between the polymorphisms and haplotypes of the MBL2 gene and the advanced PPF pattern. The MBL levels were higher in individuals with advanced fibrosis. There was risk association among high-expression haplotypes of MBL, and a protection association between the A/O Exon 1 genotype and elevated MBL serum levels. CONCLUSIONS: Our results suggest that polymorphism of Exon 1 and MBL haplotypes could potentially be used to predict the severity of advanced PPF in the Brazilian population.

Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia.

The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001).

MTR polymorphic variant A2756G and retinoblastoma risk in Brazilian children.

BACKGROUND: Polymorphisms in the genes of folate and methionine metabolism enzymes have been associated with some forms of cancer by affecting DNA synthesis, repair, and methylation. PROCEDURE: A case-control study of 72 retinoblastoma cases and 98 cancer-free children controls was performed to investigate whether the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), carrier of reduced folate 1 (RFC-1 A80G) and thymidylate synthase (TYMS 2R > 3R) altered the risk for retinoblastoma. RESULTS: MTR A2756G AG plus GG genotype frequencies were higher in patients than in controls (45% vs. 26%, P = 0.03). Individual carriers of the variant allele G had a 2.02 (95% CI: 1.05-3.92)-fold increased risk for retinoblastoma. In contrast, no association was observed with respect to MTHFR C677T and A1298C, RFC A80G, and TYMS polymorphisms. CONCLUSIONS: This study presents evidence for an association between the MTR A2756G polymorphism and retinoblastoma susceptibility in a Northeast population from Brazil.