41 research outputs found

    The analysis of candidate genes and loci involved with carotenoid metabolism in cassava (Manihot esculenta Crantz) using SLAF-seq

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    Carotenoids in cassava storage roots play important roles in benefiting people’s health in the tropics because they provide essential nutrients and antioxidants. Although the related genes and loci associated with carotenoid metabolism in many species are well reported, in cassava they are poorly understood. In the present study, GWAS base on SLAF-seq was used in detecting the related genes and loci correlated to carotenoid contents in 98 accessions from a cassava F1 mapping population. The 98 accessions were divided into four subgroups. On the basis of general linear and compressed linear models, 144 genes were detected by selective sweep analysis, and 84 SNPs and 694 genes were detected by association mapping, in which Manes.04G164700 (XanDH) and Manes.11G105300 (AAO) were probably involved in the downstream pathway of carotenoid metabolism, and their expressions in six cassava genotypes were confirmed. Our results will be useful in yellow-root cassava variety improvement and provide the most effective and sustainable approach to maximize the nutritional and health benefits of carotenoid to a large number of populations

    Detailed Molecular and Immune Marker Profiling of Archival Prostate Cancer Samples Reveals an Inverse Association between TMPRSS2:ERG Fusion Status and Immune Cell Infiltration

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    Prostate cancer is a significant global health issue and limitations to current patient management pathways often result in over- or under-treatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow utilizing an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA-Seq, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA-seq in 27/27 cases and a significantly higher TIL count was noted in tumors without a TMPRSS2:ERG fusion compared to those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n=436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-High and TIL-Low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1/27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion positive tumors. Detailed profiling, as shown here, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort

    Physical losses could partially explain modest carotenoid retention in dried food products from biofortified cassava

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    Gari, a fermented and dried semolina made from cassava, is one of the most common foods in West Africa. Recently introduced biofortified yellow cassava containing provitamin A carotenoids could help tackle vitamin A deficiency prevalent in those areas. However there are concerns because of the low retention of carotenoids during gari processing compared to other processes (e.g. boiling). The aim of the study was to assess the levels of true retention in trans–β-carotene during gari processing and investigate the causes of low retention. Influence of processing step, processor (3 commercial processors) and variety (TMS 01/ 1371; 01/1368 and 01/1412) were assessed. It was shown that low true retention (46% on average) during gari processing may be explained by not only chemical losses (i.e. due to roasting temperature) but also by physical losses (i.e. due to leaching of carotenoids in discarded liquids): true retention in the liquid lost from grating negatively correlated with true retention retained in the mash (R = -0.914). Moreover, true retention followed the same pattern as lost water at the different processing steps (i.e. for the commercial processors). Variety had a significant influence on true retention, carotenoid content, and trans-cis isomerisation but the processor type had little effect. It is the first time that the importance of physical carotenoid losses was demonstrated during processing of biofortified crops

    Coordinated Activation of Candidate Proto-Oncogenes and Cancer Testes Antigens via Promoter Demethylation in Head and Neck Cancer and Lung Cancer

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    Background: Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. Methodology/Principal Findings: We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. Conclusions/Significance: Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs i

    Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre-and post-treatment prostatic biopsies from patients with advanced prostate cancer

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    Background: Although chemotherapy for prostate cancer (PCa) can improve patient survival, some tumours are chemo-resistant. Tumour molecular profiles may help identify the mechanisms of drug action and identify potential prognostic biomarkers. We performed in vivo transcriptome profiling of pre- and post-treatment prostatic biopsies from patients with advanced hormone-naive prostate cancer treated with docetaxel chemotherapy and androgen deprivation therapy (ADT) with an aim to identify the mechanisms of drug action and identify prognostic biomarkers. Methods: RNA sequencing (RNA-Seq) was performed on biopsies from four patients before and ~22 weeks after docetaxel and ADT initiation. Gene fusion products and differentially-regulated genes between treatment pairs were identified using TopHat and pathway enrichment analyses undertaken. Publically available datasets were interrogated to perform survival analyses on the gene signatures identified using cBioportal. Results: A number of genomic rearrangements were identified including the TMPRSS2/ERG fusion and 3 novel gene fusions involving the ETS family of transcription factors in patients, both pre and post chemotherapy. In total, gene expression analyses showed differential expression of at least 2 fold in 575 genes in post-chemotherapy biopsies. Of these, pathway analyses identified a panel of 7 genes (ADAM7, FAM72B, BUB1B, CCNB1, CCNB2, TTK, CDK1), including a cell cycle-related geneset, that were differentially-regulated following treatment with docetaxel and ADT. Using cBioportal to interrogate the MSKCC-Prostate Oncogenome Project dataset we observed a statistically-significant reduction in disease-free survival of patients with tumours exhibiting alterations in gene expression of the above panel of 7 genes (p = 0.015). Conclusions: Here we report on the first “real-time” in vivo RNA-Seq-based transcriptome analysis of clinical PCa from pre- and post-treatment TRUSS-guided biopsies of patients treated with docetaxel chemotherapy plus ADT. We identify a chemotherapy-driven PCa transcriptome profile which includes the down-regulation of important positive regulators of cell cycle progression. A 7 gene signature biomarker panel has also been identified in high-risk prostate cancer patients to be of prognostic value. Future prospective study is warranted to evaluate the clinical value of this panel

    Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

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    Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit
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