Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0630-1) contains supplementary material, which is available to authorized users.
The authors evaluated adverse effects of intracarotid propofol injection during a Wada test and their risk factors in 58 patients. Nineteen patients had an adverse effect, mostly in patients receiving more than 10 mg. For patients older than age 55 years or those requiring an injection dose greater than 20 mg to produce hemiplegia, propofol should be injected slowly and patients monitored for excitatory movements.
Brassica rapa L. is an important vegetable and oilseed crop. We investigated the distribution of the histone mark tri-methylation of H3K27 (H3K27me3) in B. rapa and its role in the control of gene expression at two stages of development (2-day cotyledons and 14-day leaves) and among paralogs in the triplicated genome. H3K27me3 has a similar distribution in two inbred lines, while there was variation of H3K27me3 sites between tissues. Sites that are specific to 2-day cotyledons have increased transcriptional activity, and low levels of H3K27me3 in the gene body region. In 14-day leaves, levels of H3K27me3 were associated with decreased gene expression. In the triplicated genome, H3K27me3 is associated with paralogs that have tissue-specific expression. Even though B. rapa and Arabidopsis thaliana are not closely related within the Brassicaceae, there is conservation of H3K27me3-marked sites in the two species. Both B. rapa and A. thaliana require vernalization for floral initiation with FLC being the major controlling locus. In all four BrFLC paralogs, low-temperature treatment increases H3K27me3 at the proximal nucleation site reducing BrFLC expression. Following return to normal temperature growth conditions, H3K27me3 spreads along all four BrFLC paralogs providing stable repression of the gene.
There is a wide variation of flowering time among lines of Brassica rapa L. Most B. rapa leafy (Chinese cabbage etc.) or root (turnip) vegetables require prolonged cold exposure for flowering, known as vernalization. Premature bolting caused by low temperature leads to a reduction in the yield/quality of these B. rapa vegetables. Therefore, high bolting resistance is an important breeding trait, and understanding the molecular mechanism of vernalization is necessary to achieve this goal. In this study, we demonstrated that BrFRIb functions as an activator of BrFLC in B. rapa. We showed a positive correlation between the steady state expression levels of the sum of the BrFLC paralogs and the days to flowering after four weeks of cold treatment, suggesting that this is an indicator of the vernalization requirement. We indicate that BrFLCs are repressed by the accumulation of H3K27me3 and that the spreading of H3K27me3 promotes stable FLC repression. However, there was no clear relationship between the level of H3K27me3 in the BrFLC and the vernalization requirement. We also showed that if there was a high vernalization requirement, the rate of repression of BrFLC1 expression following prolonged cold treatments was lower.
The anteroposteriorly running superior longitudinal fasciculus could cause complications in the fiber tracking of upper-extremity motor pathways at the level of the corona radiata. During resection of tumors located near the corona radiata, subcortical electrical stimulation should be applied at some distance from the pyramidal tract, as estimated by fiber tracking.
Brassica rapa L. is an important agricultural crop that requires a period of prolonged cold for flowering. This process is known as vernalization. Studies have shown that long noncoding RNAs (lncRNAs) play important roles in abiotic stress responses and several cold-responsive noncoding RNAs have been suggested to be involved in vernalization. We examined the transcriptome of the Chinese cabbage inbred line ( B. rapa L. var. pekinensis ) RJKB-T24, and identified 1,444 long intergenic noncoding RNAs (lincRNAs), 551 natural antisense transcripts (NATs), and 93 intronic noncoding RNAs (incRNAs); 549 of the 2,088 lncRNAs significantly altered their expression in response to four weeks of cold treatment. Most differentially expressed lncRNAs did not lead to a change of expression levels in mRNAs covering or near lncRNAs, suggesting that the transcriptional responses to four weeks of cold treatment in lncRNA and mRNA are independent. However, some differentially expressed mRNAs had NATs with expression altered in the same direction. These genes were categorized as having an abiotic stress response, suggesting that the paired-expression may play a role in the transcriptional response to vernalization or cold treatment. We also identified short-term cold treatment induced NATs in BrFLC and BrMAF genes, which are involved in vernalization. The lncRNAs we identified differed from those reported in Arabidopsis thaliana , suggesting the role of lncRNAs in vernalization differ between these two species.
We attempted to establish a magnetic resonance imaging (MRI)-based radiomic model for stratifying prognostic subgroups of newly diagnosed glioblastoma (GBM) patients and predicting O (6)-methylguanine-DNA methyltransferase promotor methylation (pMGMT-met) status of the tumor. Preoperative MRI scans from 201 newly diagnosed GBM patients were included in this study. A total of 489 texture features including the first-order feature, second-order features from 162 datasets, and location data from 182 datasets were collected. Supervised principal component analysis was used for prognostication and predictive modeling for pMGMT-met status was performed based on least absolute shrinkage and selection operator regression. 22 radiomic features that were correlated with prognosis were used to successfully stratify patients into high-risk and low-risk groups (p = 0.004, Log-rank test). The radiomic high- and low-risk stratification and pMGMT status were independent prognostic factors. As a matter of fact, predictive accuracy of the pMGMT methylation status was 67% when modeled by two significant radiomic features. A significant survival difference was observed among the combined high-risk group, combined intermediate-risk group (this group consists of radiomic low risk and pMGMT-unmet or radiomic high risk and pMGMT-met), and combined low-risk group (p = 0.0003, Log-rank test). Radiomics can be used to build a prognostic score for stratifying high- and low-risk GBM, which was an independent prognostic factor from pMGMT methylation status. On the other hand, predictive accuracy of the pMGMT methylation status by radiomic analysis was insufficient for practical use.
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