scholarly journals Characterization and prognostic significance of alternative splicing events in lower‐grade diffuse gliomas

2020 ◽  
Vol 24 (22) ◽  
pp. 13171-13180
Author(s):  
Zheng Zhao ◽  
Guan‐Zhang Li ◽  
Yu‐Qing Liu ◽  
Ruo‐Yu Huang ◽  
Kuan‐Yu Wang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Prognostic Significance ◽  
Lower Grade ◽  
Diffuse Gliomas ◽  
Alternative Splicing Events

PL02.4.A Chromosome 1p19q codeletion frequency, but not survival, varies according to the IDH mutation subtypes: analysis of 1050 IDH-mutated diffuse gliomas

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
A Picca ◽  
G Berzero ◽  
A Di Stefano ◽  
N Trabelsi ◽  
F Bielle ◽  
...  
Keyword(s):  
Performance Status ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Molecular Data ◽  
Homozygous Deletion ◽  
Lower Grade ◽  
Idh Mutation ◽  
Biological Behaviour ◽  
Survival Difference ◽  
Diffuse Gliomas

Abstract BACKGROUND recurring hotspot mutations in isocitrate dehydrogenase (IDH) 1 enzymes, and to a lesser extent IDH2, are the main oncogenic alteration in most of lower-grade diffuse gliomas and a subset of grade 4 gliomas. Although most commonly represented by the IDH1R132H mutation, non-canonical IDH1/2-nonR132H mutations are present in about 10% of cases. As the neomorphic enzymatic activity can vary depending on the type of the hotspot mutation, a different biological behaviour may be inferred. Nevertheless, the prognostic significance of the different IDH1/2 mutations remains a matter of debate. MATERIAL AND METHODS we queried the OncoNeuroTek tumor bank (Pitié-Salpêtrière Hospital, Paris) to identify all registered cases of IDH-mutated diffuse gliomas. Most relevant clinical and molecular data were collected. RESULTS We identified 1050 IDH mutated diffuse gliomas (481 grade 2 [46%], 459 grade 3 [44%], and 110 grade 4 [10%]), of which 1007 (96%) were IDH1 mutated (934 IDH1R132H [89%] and 73 IDH-nonR132H [7%]) and 43 (4%) were IDH2 mutated (24 IDH2R172K [2%] and 19 IDH2-nonR172K [2%]). The chromosomes 1p/19q codeletion was more frequent in IDH2-mutated tumors (25/42 [60%] versus 350/918 [38%] in IDH1-mutated cases, p=0.005). Nevertheless, only IDH2R172K mutation was associated with the codeletion (18/24 [75%], versus 7/18 [39%] in IDH2-nonR172K-mutated tumors, p=0.02). IDH1-nonR132H tumors showed the lowest rate of 1p/19q codeletion (9/69 [13%], versus 341/849 [40%] in IDH1R132H-mutated cases, p<0.001). At the time of observation, 536 patients were deceased (51%), with a median overall survival (OS) of 115 months (mo., 95% CI 108–125 mo.). Median follow up for censored patients was 77 mo. Codeleted patients had a significantly longer OS compared to non-codeleted ones (179 vs. 96 mo., p<0.001). No significant differences in survival were seen when stratifying according to IDH mutation type (115 mo. for IDH1R132H vs. 136 mo. for IDH1-nonR132H vs. 112 mo. for IDH2R172K vs. 150 mo. for IDH2-nonR172K, p=0.8). No differences were seen when restricting the analysis to codeleted or not-codeleted patients only, respectively. In a multivariate analysis including the main prognostic factors (age, sex, preoperative performance status, tumor grade, surgical resection, midline location, 1p/19q codeletion, and p16 homozygous deletion), no survival difference was associated with any of the IDH mutation subtype. CONCLUSION although significantly different rates of 1p/19q codeletion were seen according to the four main IDH mutation subgroups, these groups does not associate with different survival profiles in our cohort.

scholarly journals Genome-Wide Profiling and Clinical Significance of Alternative Splicing Events in Glioblastoma

2020 ◽  
Author(s):  
Xiufang Ren ◽  
Tianqi Liu ◽  
Xin Chen ◽  
Gefei Guan ◽  
Cunyi Zou ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Clinical Significance ◽  
Immune Cell ◽  
Sequence Data ◽  
Prognostic Significance ◽  
Interaction Network ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Genome Wide ◽  
Alternative Splicing Events

Abstract Aims: The purpose of this study was to depict alternative splicing (AS) profiles in GBM and identify their clinical significance in the progression of GBM. Materials and Methods: RNA sequence data and clinical information were downloaded from The Cancer Genome Atlas portal (https://portal.gdc.cancer.gov/projects). Genome-wide alternative splicing events were obtained using SpliceSeq tool. Analyses were performed using GraphPad Prism 7 and R software. Key findings: Univariate Cox analysis identified 2406 AS events with prognostic significance. We built an interaction network based on these survival-related AS events. Unsupervised clustering analysis showed that patients in cluster 2 had a better prognosis than those in other clusters. The prognostic splicing factors and AS events were used to generate a splicing network. Seven prognostic signatures, developed based on the top three survival-related AS events, predicted the survival risk and may serve as independent indicators of unfavorable prognosis. Among these risk signatures, only the alternate promoter (AP) signature was upregulated in the mesenchymal subtype, which is characterized by a complex immune microenvironment. A high AP risk score indicated an overloaded local immune response and enriched immune cell infiltration, which may accelerate the progression of GBM.Significance: AS-related signatures may serve as predictors of prognosis as well as provide treatment targets and guidance for GBM patients.

Systematic Profiling of Alternative Splicing in Lower-Grade Diffuse Gliomas

2018 ◽  
Author(s):  
Fan Wu ◽  
Chuanbao Zhang ◽  
Rui-Chao Chai ◽  
Yu-Qing Liu ◽  
Zheng Zhao ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Lower Grade ◽  
Diffuse Gliomas

scholarly journals Prognostic significance of survival-associated alternative splicing events in gastric cancer

Aging ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 21923-21941
Author(s):  
Shichao Zhang ◽  
Zuquan Hu ◽  
Yingwu Lan ◽  
Jinhua Long ◽  
Yun Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alternative Splicing ◽  
Prognostic Significance ◽  
Alternative Splicing Events

scholarly journals GENE-49. RNA PROCESSING GENES CHARACTERIZE RNA SPLICING AND FURTHER STRATIFY LOWER-GRADE GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi108-vi108
Author(s):  
Rui-Chao Chai ◽  
tao jiang ◽  
Yong-Zhi Wang
Keyword(s):  
Alternative Splicing ◽  
Risk Score ◽  
Rna Processing ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Validation Dataset ◽  
Lower Grade ◽  
Aberrant Expression ◽  
Alternative Splicing Events ◽  
Genome Atlas

Abstract Aberrant expression of RNA processing genes may drive the alterative RNA profile in lower-grade gliomas (LGGs). Thus, we aimed to further stratify LGGs based on the expression of RNA processing genes. This study included 446 LGGs from The Cancer Genome Atlas (TCGA, training set) and 171 LGGs from the Chinese Glioma Genome Atlas (CGGA, validation set). The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was conducted to develop a risk-signature. The ROC curves and Kaplan–Meier curves were used to study the prognosis value of the risk-signature. Among the tested 784 RNA processing genes, 276 were significantly correlated with the OS of LGGs. Further LASSO Cox regression identified a 19-gene risk-signature, whose risk score was also an independently prognosis factor (P< 0.0001, multiplex Cox regression) in the validation dataset. The signature had better prognostic value than the traditional factors “age”, “grade” and “WHO 2016 classification” for 3‐ and 5‐year survival both two datasets (AUCs > 85%). Importantly, the risk-signature could further stratify the survival of LGGs in specific subgroups of WHO 2016 classification. Furthermore, alternative splicing events for genes such as EGFR and FGFR were found to be associated with the risk score. RNA expression levels for genes, which participated in cell proliferation and other processes, were significantly correlated to the risk score. Our results highlight the role of RNA processing genes for further stratifying the survival of patients with LGGs and provide insight into the alternative splicing events underlying this role.

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