Transcription profiling of human grade II gliomas of three hystological subtypes
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ABSTRACT: Gene expression profiling of 23 grade II gliomas of different histological subtype. Analyses was done on 9 astrocytomas, 8 oligoastrocytomas and 6 oligodendrogliomas.
Project description:Gene expression profiling of 23 grade II gliomas of different histological subtype. Analyses was done on 9 astrocytomas, 8 oligoastrocytomas and 6 oligodendrogliomas.
Project description:In this study we performed gene expression profiling of 14 cases of grade II gliomas. The results of these analysis were used in unsupervised analyses to compare correlations between the histological subtype of grade II gliomas and gene expression profiles Total RNA was isolated from 14 tumor tissue of patients, which included 5 astrocytomas WHO grade II (T2), 5 oligodendro-gliomas WHO grade II (T2) and 4 ependymomas WHO grade II (T2) samples, in additional to 4 normal tissues. The genome-wide expression analysis was first performed by directly comparing the expression profile of highly enriched different kinds of grade II gliomas and normal tissues, we then applied various data-mining methods to process the 14 different types of grade II gliomas tissues sample.
Project description:In this study we performed gene expression profiling of 14 cases of grade II gliomas. The results of these analysis were used in unsupervised analyses to compare correlations between the histological subtype of grade II gliomas and gene expression profiles
Project description:In this study we performed gene expression profiling of 14 cases of grade II gliomas. The results of these analysis were used in unsupervised analyses to compare correlations between the histological subtype of grade II gliomas and gene expression profiles Total RNA was isolated from 14 tumor tissue of patients, which included 5 astrocytomas WHO grade II (T2), 5 oligodendro-gliomas WHO grade II (T2) and 4 ependymomas WHO grade II (T2) samples, in additional to 4 normal tissues. The genome-wide expression analysis was first performed by directly comparing the expression profile of highly enriched different kinds of grade II gliomas and normal tissues, we then applied various data-mining methods to process the 14 different types of grade II gliomas tissues sample.
Project description:A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). In high grade gliomas, 1p19q codeletion and EGFR amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with EGFR amplification, identified by CGH-array. The two groups of gliomas exhibited very different gene expression profiles and were consistently distinguished by unsupervised clustering analysis. One of the most striking differences was the expression of normal brain genes by oligodendrogliomas with 1p19q codeletion. These gliomas harbored a gene expression profile that partially resembled the gene expression of normal brain samples, whereas gliomas with EGFR amplification expressed many genes in common with glioblastoma cancer stem cells. The differences between the two types of gliomas and the expression of neuronal genes in gliomas with 1p19q codeletion were both validated in an independent series of 16 gliomas using real-time RT-PCR with a set of 22 genes differentiating the two groups of gliomas (AKR1C3, ATOH8, BMP2, C20orf42, CCNB1, CDK2, CHI3L1, CTTNBP2, DCX, EGFR, GALNT13, GBP1, IGFBP2, IQGAP1, L1CAM, NCAM1, NOG, OLIG2, PDPN, PLAT, POSTN, RNF135). Immunohistochemical study of the most differentially expressed neuronal gene, alpha-internexin, clearly differentiated the two groups of gliomas, with 1p19q codeletion gliomas showing specific staining in tumor cells. These findings provide evidence for neuronal differentiation in oligodendrogliomas with 1p19q codeletion and support the hypothesis that the cell of origin for gliomas with 1p19q codeletion could be a bi-potential progenitor cell, able to give rise to both neurons and oligodendrocytes.
Project description:Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV) based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted. This signature clustered the training cohort into two classes of low and high risk of progression and death, and similarly clustered two external independent test cohorts of 104 and 73 grade II/III patients. A 22-gene class predictor of the training clusters optimally distinguished poor from good prognosis patients (median survival of 13-20 months versus over 6 years) in the validation cohorts. This classification was stronger at predicting outcome than the WHO grade II/III classification (P?2.8E-10 versus 0.018). When compared to other prognosis factors (histological subtype and genetic abnormalities) in a multivariate analysis, the 22-gene predictor remained significantly associated with overall survival. Early prediction of high risk patients (3% of WHO grade II), and low risk patients (29% of WHO grade III) in clinical routine will allow the development of more appropriate follow-up and treatments.
Project description:BackgroundGrade II and III gliomas have variable clinical behaviors, showing the distinct molecular genetic alterations from glioblastoma (GBM), many of which eventually transform into more aggressive tumors. Since the classifications of grade II/III gliomas based on the genetic alterations have been recently emerging, it is now a trend to include molecular data into the standard diagnostic algorithm of glioma.MethodsHere we sequenced TERT promoter mutational status (TERTp-mut) in the DNA of 377 grade II/III gliomas and analyzed the clinical factors, molecular aberrations, and transcriptome profiles.ResultsWe found that TERTp-mut occurred in 145 of 377 grade II and III gliomas (38.5%), mutually exclusive with a TP53 mutation (TP53-mut; P < .001) and coincident with a 1p/19q co-deletion (P = .002). TERTp-mut was an independent predictive factor of a good prognosis in all patients (P = .048). It has been an independent factor associated with a good outcome in the IDH mutation (IDH-mut) subgroup (P = .018), but it has also been associated with a poor outcome in the IDH wild-type (IDH-wt) subgroup (P = .049). Combining TERTp-mut and IDH-mut allowed the grade II/III malignancies to be reclassified into IDH-mut/TERTp-mut, IDH-mut only, TERTp-mut only, and IDH-wt/TERTp-wt. 1p/19q co-deletion, TP53-muts, Ki-67 expression differences, and p-MET expression differences characterized IDH-mut/TERTp-mut, IDH-mut only, TERTp-mut only, and IDH-wt/TERTp-wt subtypes, respectively.ConclusionsOur results showed that TERTp-mut combined with IDH-mut allowed simple classification of grade II/III gliomas for stratifying patients and clarifying diagnostic accuracy by supplementing standard histopathological criteria.
Project description:BackgroundLower-grade gliomas (LGGs) show highly metabolic heterogeneity and adaptability. To develop effective therapeutic strategies targeting metabolic processes, it is necessary to identify metabolic differences and define metabolic subtypes. Here, we aimed to develop a classification system based on metabolic gene expression profile in LGGs.MethodsThe metabolic gene profile of 402 diffuse LGGs from the Cancer Genome Atlas (TCGA) was used for consensus clustering to determine robust clusters of patients, and the reproducibility of the classification system was evaluated in three Chinese Glioma Genome Atlas (CGGA) cohorts. Then, the metadata set for clinical characteristics, immune infiltration, metabolic signatures and somatic alterations was integrated to characterise the features of each subtype.ResultsWe successfully identified and validated three highly distinct metabolic subtypes in LGGs. M2 subtype with upregulated carbohydrate, nucleotide and vitamin metabolism correlated with worse prognosis, whereas M1 subtype with upregulated lipid metabolism and immune infiltration showed better outcome. M3 subtype was associated with low metabolic activities and displayed good prognosis. Three metabolic subtypes correlated with diverse somatic alterations. Finally, we developed and validated a metabolic signature with better performance of prognosis prediction.ConclusionsOur study provides a new classification based on metabolic gene profile and highlights the metabolic heterogeneity within LGGs.
Project description:Background and purpose Lower-grade gliomas (LGG) exhibit a wide range of metabolic pathway changes, and metabolic reprogramming can be largely seen as a result of oncogenic driving events. Glycolysis, an important pathway of tumor energy source, has been poorly studied in gliomas. The aim of this article is to analyze the relationship between glycolysis and lower-grade glioma development and prognosis in order to explore the heterogeneous relevance of glycolysis in lower-grade gliomas. Methods and results Our study searched the TCGA database and identified three glycolytic subtypes with significant prognostic differences by unsupervised clustering analysis of core glycolytic genes, named C1, C2, and C3. By analysis of clinical prognosis, somatic cell variation, and immune infiltration, we found that C3 had the best prognosis with molecular features of IDHmut-codel, followed by C1 with major molecular features of IDHmut-non-codel, G -CIMP high subtype, while C2 had the worst prognosis, mainly exhibiting IDHwt, G-CIMP low and mesenchymal-like subtypes with seven important CNV features, including CDKN2A/B deletion, chr7 gain and chr10 deletion, chr19/20 co-gain, EGFR amplification and PDGFRA/B deletion phenotypes were significantly increased, with the highest level of stemness and significant T-cell depletion features. Finally, to quantify the level of abnormal glycolysis and its impact on prognosis, we developed GlySig to reflect the glycolytic activity of LGG and integrated molecular features to construct nomogram that can be independently assessed to predict prognosis. Conclusions Our study analyzed the tumor characteristics of different glycolytic states, and our findings explain and describe the heterogeneity of glycolytic metabolism within diffuse LGGs.