Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population.

Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean population. For this purpose, we obtained base data resulting from a GWAS on BMI using 57,110 HEXA study subjects from the Korean Genome and Epidemiology Study (KoGES). Subsequently, we calculated PRSs in 13,504 target subjects from the KARE and CAVAS studies of KoGES using the PRSice-2 software. The best-fit PRS for BMI (PRSBMI) comprising 53,341 SNPs was selected at a p-value threshold of 0.064, at which the model fit had the greatest R2 score. The PRSBMI was tested for its association with obesity-related quantitative traits and diseases in the target dataset. Linear regression analyses demonstrated significant associations of PRSBMI with BMI, blood pressure, and lipid traits. Logistic regression analyses revealed significant associations of PRSBMI with obesity, hypertension, and hypo-HDL cholesterolemia. We observed about 2-fold, 1.1-fold, and 1.2-fold risk for obesity, hypertension, and hypo-HDL cholesterolemia, respectively, in the highest-risk group in comparison to the lowest-risk group of PRSBMI in the test population. We further detected approximately 26.0%, 2.8%, and 3.9% differences in prevalence between the highest and lowest risk groups for obesity, hypertension, and hypo-HDL cholesterolemia, respectively. To predict the incidence of obesity and related diseases, we applied PRSBMI to the 16-year follow-up data of the KARE study. Kaplan-Meier survival analysis showed that the higher the PRSBMI, the higher the incidence of dyslipidemia and hypo-HDL cholesterolemia. Taken together, this study demonstrated that a PRS developed for BMI may be a valuable indicator to assess the risk of obesity and related diseases in the Korean population.

Clinicopathologic and Molecular Characteristics of and Diagnostic Dilemmas in Invasive Breast Carcinoma with Choriocarcinomatous Pattern apropos a New Case: A Literature Review with New Findings.

BACKGROUND: Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with ß-human chorionic gonadotropin (ß-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. METHODS: Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. RESULTS: Compared to the MC-B patients, the IBC-CP patients were older (p < 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed ß-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. CONCLUSION: The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.

Theoretical modeling of collaterally sensitive drug cycles: shaping heterogeneity to allow adaptive therapy.

In previous work, we focused on the optimal therapeutic strategy with a pair of drugs which are collaterally sensitive to each other, that is, a situation in which evolution of resistance to one drug induces sensitivity to the other, and vice versa. Yoona (Bull Math Biol 8:1-34,Yoon et al. 2018) Here, we have extended this exploration to the optimal strategy with a collaterally sensitive drug sequence of an arbitrary length, N. To explore this, we have developed a dynamical model of sequential drug therapies with N drugs. In this model, tumor cells are classified as one of N subpopulations represented as [Formula: see text]. Each subpopulation, [Formula: see text], is resistant to '[Formula: see text]' and each subpopulation, [Formula: see text] (or [Formula: see text], if [Formula: see text]), is sensitive to it, so that [Formula: see text] increases under '[Formula: see text]' as it is resistant to it, and after drug-switching, decreases under '[Formula: see text]' as it is sensitive to that drug(s). Similar to our previous work examining optimal therapy with two drugs, we found that there is an initial period of time in which the tumor is 'shaped' into a specific makeup of each subpopulation, at which time all the drugs are equally effective ([Formula: see text]). After this shaping period, all the drugs are quickly switched with duration relative to their efficacy in order to maintain each subpopulation, consistent with the ideas underlying adaptive therapy. West(Canver Res 80(7):578-589Gatenby et al. 2009) and Gatenby (Cancer Res 67(11):4894-4903West et al. 2020). Additionally, we have developed methodologies to administer the optimal regimen under clinical or experimental situations in which no drug parameters and limited information of trackable populations data (all the subpopulations or only total population) are known. The therapy simulation based on these methodologies showed consistency with the theoretical effect of optimal therapy .

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.

The 2019 mathematical oncology roadmap.

Whether the nom de guerre is Mathematical Oncology, Computational or Systems Biology, Theoretical Biology, Evolutionary Oncology, Bioinformatics, or simply Basic Science, there is no denying that mathematics continues to play an increasingly prominent role in cancer research. Mathematical Oncology-defined here simply as the use of mathematics in cancer research-complements and overlaps with a number of other fields that rely on mathematics as a core methodology. As a result, Mathematical Oncology has a broad scope, ranging from theoretical studies to clinical trials designed with mathematical models. This Roadmap differentiates Mathematical Oncology from related fields and demonstrates specific areas of focus within this unique field of research. The dominant theme of this Roadmap is the personalization of medicine through mathematics, modelling, and simulation. This is achieved through the use of patient-specific clinical data to: develop individualized screening strategies to detect cancer earlier; make predictions of response to therapy; design adaptive, patient-specific treatment plans to overcome therapy resistance; and establish domain-specific standards to share model predictions and to make models and simulations reproducible. The cover art for this Roadmap was chosen as an apt metaphor for the beautiful, strange, and evolving relationship between mathematics and cancer.

Spatial and temporal changes in myogenic protein expression by the microenvironment after freeze injury.

Skeletal muscle has the remarkable capability to regenerate itself following injury. Adult myogenic stem cells (MSCs) are responsible for the repair and regeneration, and their activity is controlled by intrinsic and extrinsic factors. The aim of this study was to examine and compare the expression levels of Pax3, Pax7, MRF and p38 proteins during the course of regeneration and in different areas of the focal freeze-lesion damaged adult rat TA muscle. Using the focal freeze injury model, immunohistochemistry, laser-capture micro-dissection and Western blot analysis were performed. The results show that (1) in the severely damaged area, the focal freeze-lesion injury significantly activated Pax7 and myogenin expression within 7 days and down-regulated Pax3, MyoD and Myf-5 within 1 or 3 days, and (2) the level of the p38 protein was strongly and transiently up-regulated in the whole muscle on day 7 following injury, whereas the level of the pp38 protein was down-regulated within 3 days in the severely damaged and non-damaged areas. These findings indicate that the temporal (e.g. the time course of regeneration) and spatial (e.g. three zones created by the focal freeze-lesion) cues in a regenerating muscle have a significant impact on the activity of the adult MSCs.

Effect of polydiacetylene-based nanosomes on cell viability and endocytosis.

Polydiacetylene-based nanoparticles have been developed as nanocarriers for various bio-applications. However, how nanocarriers enter the cell environment and affect cell viability has not yet been considerably explored. In this study, polydiacetylene-based nanoliposomes (nanosomes) were electrostatically complexed with rhodamine fluorophores. Based on real-time cell imaging and cell viability assessment, the most highly polymerized nanosomes were found to be less toxic to cells. Moreover, it was revealed that the rhodamine/polydiacetylene nanosome complex dissociates at cell environment, the polydiacetylene nanosome penetrates into cells, as suggested by the fluorescence observed in confocal microscopy images.

Effects of Rifampin and Doxycycline Treatments in Patients With Uncomplicated Scrub Typhus: An Open-Label, Randomized, Controlled Trial.

Background: Doxycycline is currently the most frequently used treatment in patients with scrub typhus. However, doxycycline-resistant strains have been found, necessitating the development of a new treatment. Rifampin is known to be effective even for such strains. Our aim in this study was to compare the effects of rifampin and doxycycline treatment in patients with scrub typhus in areas in which resistance to doxycycline has not been reported. Methods: Patients admitted to Chosun University Hospital and regional network hospitals between 2007 and 2009 with a body temperature ≥37.5°C and suspected to have scrub typhus were randomly assigned to 1 of 2 treatment groups: a group administered doxycycline 100 mg twice daily for 5 days and a group administered rifampin 600 mg once daily for 5 days. For treatment outcomes, fever, headache, muscle ache, and rash clearance times were compared between the groups. Results: The rifampin and doxycycline groups showed equivalence in all treatment outcomes evaluated. The proportions of patients with fever clearance within 48 hours were similar between groups. Furthermore, there was no significant difference in the occurrence of side effects following drug administration between groups. Conclusions: On the basis of the finding that equivalent treatment effects and safety were found in patient groups that received 600 mg of rifampin and 200 mg of doxycycline, respectively, for 5 days to treat scrub typhus, rifampin may be considered an alternative treatment to doxycycline. Clinical Trials Registration: NCT00568711.

Microsphere-Based Nanoindentation for the Monitoring of Cellular Cortical Stiffness Regulated by MT1-MMP.

Biophysical properties are intimately connected to metastatic functions and aggressiveness in cancers. Especially, cellular stiffness is regarded as a biomarker for the understanding of metastatic potential and drug sensitivity. Here, protease-mediated changes of cortical stiffness are identified due to the deformation of cytoskeleton alignment at a cortex. For the past few decades, membrane type 1-matrix metalloproteinase (MT1-MMP) has been well known as a kernel protease enriched in podosomes during metastasis for extracellular matrix degradation. However, the biophysical significance of MT1-MMP expressing cancer cells is still unknown. Therefore, the nanomechanics of cancer cells is analyzed by a nanoindentation using a microsphere-attached cantilever of atomic force microscopy (AFM). In conclusion, the results suggest that MT1-MMP has contributed as a key regulator in cytoskeletal deformation related with cancer metastasis. Particularly, the AFM-based nanoindentation system for the monitoring of cortical nanomechanics will be crucial to understand molecular networks in cancers.

Hemorrhagic fever with renal syndrome accompanied by panhypopituitarism and central diabetes insipidus: a case report.

Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal.

Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery.

BACKGROUND: Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. METHODS: Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow-derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γcnull mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging. RESULTS: MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS. DISCUSSION: These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients.

A case report of scrub typhus complicated with myocarditis and rhabdomyolysis.

BACKGROUND: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, a gram-negative intracellular bacterium. Myocarditis and rhabdomyolysis are rare complications of scrub typhus. CASE PRESENTATION: We report a case of scrub typhus, which was simultaneously complicated with myocarditis and rhabdomyolysis. A 54-year-old woman presented to our hospital with myalgia in the upper and lower limbs, oedema and a fever of 7 days' duration. We confirmed the diagnosis of scrub typhus complicated with myocarditis by pericardial fluid analysis and cardiac magnetic resonance imaging results. The pericardial fluid showed characteristics of an exudate, an elevated immunofluorescence assay (IFA) IgG titer of 1:2048 and a positive 16S rRNA qPCR result. We also diagnosed rhabdomyolysis by the patient's presenting symptoms, elevated muscle enzyme levels and bone scan results. CONCLUSION: We report for the first time a case of scrub typhus complicated with both myocarditis and rhabdomyolysis, the causative agent of which was the Boryong genotype of O. tsutsugamushi.

Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs.

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, [Formula: see text] and [Formula: see text], each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for [Formula: see text] and [Formula: see text], we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., [Formula: see text]-long for DrugA and [Formula: see text]-long for DrugB with [Formula: see text] and [Formula: see text]). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, [Formula: see text], and the effect of each drug. We determine a critical ratio, which we term [Formula: see text], at which the two drugs are equally effective. As the first stage of the optimal strategy is applied, [Formula: see text] changes monotonically to [Formula: see text] and then, during the second stage, remains at [Formula: see text] thereafter. Beyond our analytic results, we explored an individual-based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.

MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs.

Mesenchymal stem or stromal cells (MSCs) have many potential therapeutic applications including therapies for cancers and tissue damages caused by cancers or radical cancer treatments. However, tissue-derived MSCs such as bone marrow MSCs (BM-MSCs) may promote cancer progression and have considerable donor variations and limited expandability. These issues hinder the potential applications of MSCs, especially those in cancer patients. To circumvent these issues, we derived MSCs from transgene-free human induced pluripotent stem cells (iPSCs) efficiently with a modified protocol that eliminated the need of flow cytometric sorting. Our iPSC-derived MSCs were readily expandable, but still underwent senescence after prolonged culture and did not form teratomas. These iPSC-derived MSCs homed to cancers with efficiencies similar to BM-MSCs but were much less prone than BM-MSCs to promote the epithelial-mesenchymal transition, invasion, stemness, and growth of cancer cells. The observations were probably explained by the much lower expression of receptors for interleukin-1 and TGFß, downstream protumor factors, and hyaluronan and its cofactor TSG6, which all contribute to the protumor effects of BM-MSCs. The data suggest that iPSC-derived MSCs prepared with the modified protocol are a safer and better alternative to BM-MSCs for therapeutic applications in cancer patients. The protocol is scalable and can be used to prepare the large number of cells required for "off-the-shelf" therapies and bioengineering applications.

Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice.

Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade.

Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease-free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. © 2016 Wiley Periodicals, Inc.

First report of iliacus abscess caused by Salmonella enterica serovar Othmarschen.

The non-typhoidal bacterium Salmonella enterica subspecies enterica serovar Othmarschen (Salmonella Othmarschen) is a rare human pathogen. Abscess formation due to non-typhoidal Salmonella infections is a very rare complication in this antibiotic era. We report the first case of iliacus abscess after a short period of gastroenteritis which was caused by non-typhoidal Salmonella enterica belonging to group C1, serovar Othmarschen in a patient without any underlying conditions. A young female presented in our hospital complaining of pain in right hip joint area. She gave a history of watery diarrhea 3 days before the onset of pain. On examination the patient was ill-looking and there was tenderness in the right hip joint area. S. enterica was identified using 16S rRNA gene amplification by PCR and serotyped to be serovar Othmarschen from the pus sample of iliacus abscess. This is the first reported case of iliacus abscess due to Salmonella serover Othmarschen infection. Our case suggests that S. enterica serovar Othmarschen can cause severe focal infections associated with gastroenteritis. The literature on the rare association of Salmonella enterica and abscess formation is reviewed.

Pre-activated human mesenchymal stromal cells in combination with doxorubicin synergistically enhance tumor-suppressive activity in mice.

BACKGROUND AIMS: Previously, we showed that human mesenchymal stromal cells (hMSCs) were activated to express tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) upon TNF-α stimulation, induced cell death in triple-negative breast cancer (TNBC) MDA-MB-231 cells (MDA), and RNA released from apoptotic MDA further increased TRAIL expression in hMSCs. This feed-forward stimulation increased apoptosis in MDA cells. Here, we tested whether TRAIL-expressing hMSCs, in combination with a sub-toxic-dose of a chemotherapy drug doxorubicin, would overcome TRAIL resistance and create synergistic effects on targeting metastatic TNBC. METHODS: To optimize conditions for the combination treatment, we (i) selected an optimal condition to activate hMSCs for TRAIL expression, (ii) selected an optimal dose of doxorubicin treatment, (iii) examined underlying mechanisms in vitro and (iv) tested the efficacy of the optimized conditions in a xenograft mouse model of human breast cancer lung metastasis. RESULTS: The results showed that DNA fragments from apoptotic MDA triggered hMSCs to increase further TRAIL expression in an absent in melanoma 2 (AIM2)-dependent manner, and thus higher TRAIL-expressing hMSCs stimulated with synthetic DNA, poly(deoxyadenylic-deoxythymidylic) acid [poly(dA:dT)], more effectively suppressed tumor progression in vivo. Furthermore, activated hMSCs increased apoptosis in MDA cells when combined with a sub-toxic dose of doxorubicin, which was mediated by up-regulating TRAIL and Fas-related pathways. When we combined the optimized conditions, pre-activated hMSCs with poly (dA:dT) synergistically reduced tumor burden even with minimal doxorubicin treatment in a xenograft mouse model of human breast cancer lung metastasis. CONCLUSIONS: These results suggest that the treatment of hMSCs with a sub-toxic dose of doxorubicin can overcome TRAIL resistance and be a potential novel therapy for TNBC metastasis treatment.

BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas.

BACKGROUND: BRAF mutation has received a great deal of attention in neuro-oncology field, recently. This study aimed to investigate the incidence and the clinical significance of BRAF(V600E) in low-grade glial tumors. METHODS: An institutional cohort of 105 brain tumors (51 dysembryoplastic neuroepithelial tumors (DNTs), 14 subependymal giant cell astrocytomas (SEGAs), 12 glioblastoma with neuronal marker expression (GBM-N), and 28 pleomorphic xanthoastrocytomas (PXAs)) from 100 patients were investigated for the presence of BRAF(V600E) by direct sequencing. RESULTS: We found frequent BRAF(V600E) in DNTs (26/51, 51%), SEGAs (6/14, 42.9%), and PXAs (14/28, 50%). In DNTs, BRAF(V600E) was more commonly detected in tumors with extra-temporal location (68.2% vs. 37.9%; P = 0.032). The diagnostic subgroups of tuberous sclerosis complex were not correlated with BRAF(V600E) in patients with SEGA (P = 0.533). One PXA case revealed a unique duplication mutation (p.Thr599dup) of codon 599. All GMB-N cases did not carry BRAF mutation. CONCLUSIONS: Our data indicate that BRAF(V600E) is a common genetic alteration in low-grade glial tumors with neuronal component or differentiation. High frequency of BRAF(V600E) in DNTs and SEGAs would be useful in the differential diagnosis, and also offers a potential specific treatment targeting BRAF(V600E) .