scholarly journals BRAFnon-V600E more frequently co-occurs with IDH1/2 mutation in adult patients with gliomas than patients harboring BRAFV600E, but without survival advantage

Author(s):  
Rong Da ◽  
Maode Wang ◽  
Haitao Jiang ◽  
Tuo Wang ◽  
Wei Wang

Abstract Background The effect of BRAFnon−V600E and BRAFV600E on the outcome and the molecular characteristics in adult glioma patients is unknown and needs to be explored, although BRAFV600E has been extensively studied in pediatric glioma. Methods Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were retrieved and investigated using the cBioPortal. The prognosis of available adult glioma cohorts with BRAFV600E and BRAFnon−V600E mutations was also investigated. Results Glioblastoma multiform was the most common cancer type with BRAF non−V600E and BRAFV600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAFnon−V600E than in BRAFV600E, and TP53 was the independent risk factor (56.00% vs. 7.41%). Both BRAFnon−V600E and BRAFV600E frequently overlapped with CDKN2A/2B homozygous deletions (HD), whereas there was no significant difference. Survival analysis showed no difference between BRAF non−V600E and BRAFV600E cohorts, even excluded the effects of IDH1/2 mutations, and concerned the BRAFnon−V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of BRAFnon−V600E and IDH1/2WT with mutations in the G-loop groups was the shortest. Conclusions BRAF non−V600E exhibited a higher association with IDH1/2 mutation than BRAFV600E, but no survival advantage was found.

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Wang ◽  
Maode Wang ◽  
Haitao Jiang ◽  
Tuo Wang ◽  
Rong Da

Abstract Background The effects of BRAFnon-V600E and BRAFV600E on the outcomes and the molecular characteristics of adult glioma patients are unknown and need to be explored, although BRAFV600E has been extensively studied in pediatric glioma. Methods Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were investigated using data from The Cancer Genome Atlas (TCGA) public database retrieved by cBioPortal. The prognosis of available adult glioma cohorts with BRAFV600E and BRAFnon-V600E mutations were also investigated. Results Ninety patients with BRAFV600E or BRAFnon-V600E were enrolled in this study, and data from 52 nonredundant patients were investigated. Glioblastoma multiform was the most common cancer type, with BRAFnon-V600E and BRAFV600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAFnon-V600E than in BRAFV600E, and TP53 was an independent risk factor (56.00% vs. 7.41%). Both BRAFnon-V600E and BRAFV600E frequently overlapped with CDKN2A/2B homozygous deletions (HDs), but there was no significant difference. Survival analysis showed no difference between the BRAFnon-V600E and BRAFV600E cohorts, even after excluding the survival benefit of IDH1/2 mutations and considering the BRAFnon-V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of patients with BRAFnon-V600E & IDH1/2WT with mutations in the G-loop groups was the shortest. Conclusions BRAFnon-V600E exhibited a stronger association with IDH1/2 mutations than BRAFV600E, but no survival advantage was found.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Bingran Wang ◽  
Tiancheng Lou ◽  
Lingling Wei ◽  
Wenchan Chen ◽  
Longbing Huang ◽  
...  

AbstractAlternaria alternata, a causal agent of leaf blights and spots on a wide range of hosts, has a high risk of developing resistance to fungicides. Procymidone, a dicarboximide fungicide (DCF), has been widely used in controlling Alternaria leaf blights in China for decades. However, the resistance of A. alternata against DCFs has rarely been reported from crucifer plants. A total of 198 A. alternata isolates were collected from commercial fields of broccoli and cabbage during 2018–2019, and their sensitivities to procymidone were determined. Biochemical and molecular characteristics were subsequently compared between the high-level procymidone-resistant (ProHR) and procymidone-sensitive (ProS) isolates, and also between ProHR isolates from broccoli and cabbage. Compared with ProS isolates, the mycelial growth rate, sporulation capacity and virulence of most ProHR isolates were reduced; ProHR isolates displayed an increased sensitivity to osmotic stresses and a reduced sensitivity to sodium dodecyl sulfate (SDS); all ProHR isolates showed a reduced sensitivity to hydrogen peroxide (H2O2) except for the isolate B102. Correlation analysis revealed a positive cross-resistance between procymidone and iprodione, or fludioxonil. When treated with 10 μg/mL of procymidone, both mycelial intracellular glycerol accumulations (MIGAs) and relative expression of AaHK1 in ProS isolates were higher than those in ProHR isolates. Sequence alignment of AaHK1 from ten ProHR isolates demonstrated that five of them possessed a single-point mutation (P94A, V612L, E708K or Q924STOP), and four isolates had an insertion or a deletion in their coding regions. No significant difference in biochemical characteristics was observed among ProHR isolates from two different hosts, though mutations in AaHK1 of the cabbage-originated ProHR isolates were distinct from those of the broccoli-originated ProHR isolates.


2015 ◽  
Vol 84 (5) ◽  
Author(s):  
Mirjana Rajer ◽  
Luka Čavka ◽  
Amela Duratović

ABSTRACTBACKGROUNDNowadays cancer patients tend to be more involved in the medical decision process. Active participation improves health outcomes and patient satisfaction. To participate effectively patients require a huge amount of information, but time limits make it impossible to satisfy all information needs at clinics. We tried to find out which kind of media cancer patients use when searching for information and how often. Lastly, we try to find out how popular the Internet is in this regard.METODSIn this research we invited cancer patients, who had regular clinic examinations at the Oncology Institute between 21st and 25th May in 2012. We carried out a prospective research by anonymous questionnaires. We were investigating which media were used and how often. We analysed results with descriptive statistics, ANOVA, the χ²-Test and the t-test.RESULTS478 of 919 questionnaires distributed among cancer patients were returned. Mean age was 59.9 years. 61 % of responders were female, and the most common level of education was high school (33 %). Most common cancer type was breast cancer (33 %), followed by gastrointestinal and lung cancer. Patients search for information most often on television (81.4% responders), followed by specialized brochures (78%), internet (70.8%) and newspapers (67.6%). Patients who do not use media for information searching are older than average (62.5 years vs. 59.9 years; p<0,000).CONCLUSIONSAccording to our results patients search for information most often on television, followed by brochures, internet and newspapers. Older patients less often search for information. This data might help doctors in everyday clinical practice.


2020 ◽  
Author(s):  
Kai Zhou ◽  
Anqiang Wang ◽  
Sheng Ao ◽  
Jiahui Chen ◽  
Ke Ji ◽  
...  

Abstract Background : To investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach ( HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery. Methods : We retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. The relationships between gastric cancer type and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression. Results : Our data demonstrate that there was no statistically significant difference in the OS between HAS and non-HAS {K-M, P=log rank (Mantel-Cox), (before PSM P=0.397); (1:1 PSM P=0.345); (1:2 PSM P=0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching). Conclusion : HAS was generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.


2016 ◽  
Vol 85 (2) ◽  
pp. 41-43
Author(s):  
Robert Bobotsis ◽  
Brandon Chau

Skin cancer is currently the most common cancer type afflicting North Americans today and with an aging population the incidence is likely to increase. Certain skin cancers such as melanoma can result in significant morbidity and mortality especially if not identified and treated early. The traditional ABCDE rule (asymmetric shape, irregular borders, variation in colour, diameter >6 mm and evolution/elevation of the lesion) used to identify concerning tumours will in fact miss many early melanomas. This problem is exacerbated in patients with hereditary forms of melanoma such as Familial Atypical Multiple- Mole Melanoma (FAMMM) syndrome where multiple atypical nevi satisfying the ABCDE criteria are present and would therefore warrant biopsy. Most of these biopsies would be unnecessary and would increase the patient’s morbidity. Dermatoscopy is a clinical tool that provides a bridge between clinical and histopathologic evaluation and has proven to be helpful in triaging suspicious lesions in the general population and to be a first-line screening tool to increase the detection of early melanomas in patients with FAMMM.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1501-1501
Author(s):  
Anna Jo Smith ◽  
Jeremy Applebaum ◽  
Amanda Nickles Fader

1501 Background: Under the Affordable Care Act’s 2014 Medicaid expansion, more than 12 million Americans gained health insurance. Whether such gains in insurance improve survival in gynecologic cancer is unknown. This study aims to determine whether Medicaid expansion is associated with improved survival among women with gynecologic cancers. Methods: We conducted a retrospective cohort study using a difference-in-differences study design comparing insurance status, stage at diagnosis, delays in treatment, and one-year survival before and after the ACA’s Medicaid expansion in Medicaid expansion states (intervention group) compared to women in non-expansion states (control group). Using hospital-reported data from the 2010-2016 National Cancer Database, we compared outcomes overall for women ages 40-64 years old with endometrial, cervical, ovarian, or vulva/vaginal cancer and then stratified by cancer type, stage, race, and rural/urban status. We adjusted for patient (area-level income, area-level education, distance traveled for care, comorbidities), clinical (co-morbidities, grade) and hospital (academic facility) characteristics. Results: Our sample included 241,713 women with gynecologic cancer, 119,392 in expansion states and 122,321 in non-expansion states. Post-Medicaid expansion, there was a statistically significant 0.8 % increase in 1-year survival among patients in expansion states compared to non-expansion states (95% CI 0.1-1.5). There was also a significant reduction in uninsurance (-1.1%, 95%CI, --1.5, -0.7) and delays of 30+ days from diagnosis to treatment (-2.4%, 95%CI -3.4, -1.2). There was no significant change in early-stage diagnosis (0%; 95%CI -0.7-0.7). Improvements in one-year survival after Medicaid expansion were driven by ovarian cancer (difference-in-differences 2.2%, 95%CI 0.6-3.8) and in white women (difference-in-differences 0.8%, 95%CI 0.1-1.5), while there was no significant difference in one-year survival for non-white or rural women. Conclusions: The Affordable Care Act’s Medicaid expansion was significantly associated with 1-year survival and insurance access among patients with gynecologic cancer. Insurance expansion efforts in non-Medicaid expansion states may improve survival for women with gynecologic cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Isil Yurdaisik

Objective. Breast cancer is the most common cancer type among women worldwide. Today, health consumers search the Internet to gain health information about many diseases including breast cancer. YouTube™ is the second most commonly used website on the Internet. However, the quality and accuracy of health-related YouTube™ videos are controversial. The objective of this study was to investigate the quality and accuracy of breast cancer-related videos on YouTube™. Material and Methods. “Breast cancer” keyword was entered into YouTube™ search bar, and after excluding advertisement, duplicate, and non-English videos, the first most viewed 50 videos were analyzed. Videos’ length, the number of views, comments, likes, and dislikes were recorded. DISCERN and JAMA scores and Video Power Index (VPI) values of the videos were calculated. All videos were evaluated by two independent radiologists experienced on breast cancer. The correlation between the two observers was also analyzed. Results. Of all videos, 14% were uploaded by physicians, 26% by health channels, 20% by patients, 10% by news channels, 2% by herbalists, 2% by blog channels, and 2% by nonprofit activism channels. The mean DISCERN score was calculated as 26.70±10.99 and the mean JAMA score as 2.23±0.97. The mean VPI value, which was calculated to determine the popularity of the videos, was found as 94.10±4.48. A strong statistically significant correlation was found between the two observers in terms of both DISCERN and JAMA scores. There was an excellent agreement between the two observers. Conclusion. The overall quality of the viewed videos was found as poor. Healthcare professionals should be encouraged to upload breast cancer-related videos with accurate information to promote patients for screening and direct them appropriately.


2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ajaz Bulbul ◽  
John Paul Shen ◽  
Joanne Xiu ◽  
Pablo Tamayo ◽  
Hatim Husain

Purpose Desmoplastic small round blue-cell tumors (DSRCTs) are sarcomas that contain the t(11;22) (p13;q12) translocation EWS-WT1 fusion protein. Because this is a rare tumor type, prospective clinical trials in DSRCT are challenging. Patients are treated in a manner similar to those with Ewing sarcoma; however, differences in prognosis and clinical presentation suggest fundamental differences in biology and potentially different therapeutic implications. This study aimed to characterize the molecular characteristics of DSRCT tumors to explore unique therapeutic options for this extremely rare and aggressive cancer type. Methods Thirty-five DSRCT tumors were assessed using next-generation sequencing, protein expression (immunohistochemistry), and gene amplification (chromogenic in situ hybridization or fluorescence in situ hybridization). Three patients had tumor mutational load, which was calculated as somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Gene expression data were obtained for an additional seven DSRCT tumors. Molecular alterations were compared with 88 Ewing sarcomas. Results The most common alterations that distinguished DSRCTs from Ewing sarcoma included higher androgen receptor (AR), TUBB3, epidermal growth factor receptor, and TOPO2A expression. Independent analysis by RNA sequencing confirmed higher AR expression from an independent data set of EWS-WT1 fusion–positive DSRCTs compared with Ewing sarcoma and a pan-cancer analysis. DSRCTs had somatic mutations that were identified in TP53 and FOXO3, averaged five mutations per megabase, and no programmed death-ligand 1 expression was detected in any DSRCT samples. Conclusion The current analysis provides the first comparative analysis, to our knowledge, of molecular aberrations that distinguish DSRCT from Ewing sarcoma. High AR expression seems to be a defining event in these malignancies, and additional investigation of the responsiveness of AR inhibitors in this disease is encouraged.


Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 309 ◽  
Author(s):  
Chiara Bazzichetto ◽  
Fabiana Conciatori ◽  
Claudio Luchini ◽  
Francesca Simionato ◽  
Raffaela Santoro ◽  
...  

The threatening notoriety of pancreatic cancer mainly arises from its negligible early diagnosis, highly aggressive progression, failure of conventional therapeutic options and consequent very poor prognosis. The most important driver genes of pancreatic cancer are the oncogene KRAS and the tumor suppressors TP53, CDKN2A, and SMAD4. Although the presence of few drivers, several signaling pathways are involved in the oncogenesis of this cancer type, some of them with promising targets for precision oncology. Pancreatic cancer is recognized as one of immunosuppressive phenotype cancer: it is characterized by a fibrotic-desmoplastic stroma, in which there is an intensive cross-talk between several cellular (e.g., fibroblasts, myeloid cells, lymphocytes, endothelial, and myeloid cells) and acellular (collagen, fibronectin, and soluble factors) components. In this review; we aim to describe the current knowledge of the genetic/biological landscape of pancreatic cancer and the composition of its tumor microenvironment; in order to better direct in the intrinsic labyrinth of this complex tumor type. Indeed; disentangling the genetic and molecular characteristics of cancer cells and the environment in which they evolve may represent the crucial step towards more effective therapeutic strategies


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Erdogan Taskesen ◽  
Sjoerd M. H. Huisman ◽  
Ahmed Mahfouz ◽  
Jesse H. Krijthe ◽  
Jeroen de Ridder ◽  
...  

Abstract The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a single cancer-type towards measuring several different molecular characteristics across multiple cancer-types. Although current approaches shed light on molecular characteristics of various cancer-types, detailed relationships between patients within cancer clusters are unclear. We propose a novel multi-omic integration approach that exploits the joint behavior of the different molecular characteristics, supports visual exploration of the data by a two-dimensional landscape, and inspection of the contribution of the different genome-wide data-types. We integrated 4,434 samples across 19 cancer-types, derived from TCGA, containing gene expression, DNA-methylation, copy-number variation and microRNA expression data. Cluster analysis revealed 18 clusters, where three clusters showed a complex collection of cancer-types, squamous-cell-carcinoma, colorectal cancers, and a novel grouping of kidney-cancers. Sixty-four samples were identified outside their tissue-of-origin cluster. Known and novel patient subgroups were detected for Acute Myeloid Leukemia’s, and breast cancers. Quantification of the contributions of the different molecular types showed that substructures are driven by specific (combinations of) molecular characteristics.


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