Codeletion In Gliomas Research Articles

Diagnostic test accuracy and cost-effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma.

Diagnostic test accuracy and cost-effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma.

Galectin-9/TIM-3 as a Key Regulator of Immune Response in Gliomas With Chromosome 1p/19q Codeletion.

Gliomas with chromosome 1p/19q codeletion were considered a specific tumor entity. This study was designed to reveal the biological function alterations tightly associated with 1p/19q codeletion in gliomas. Clinicopathological and RNA sequencing data from glioma patients were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Gene set variation analysis was performed to explore the differences in biological functions between glioma subgroups stratified by 1p/19q codeletion status. The abundance of immune cells in each sample was detected using the CIBERSORT analytical tool. Single-cell sequencing data from public databases were analyzed using the t-distributed stochastic neighbor embedding (t-SNE) algorithm, and the findings were verified by in vitro and in vivo experiments and patient samples.We found that the activation of immune and inflammatory responses was tightly associated with 1p/19q codeletion in gliomas. As the most important transcriptional regulator of Galectin-9 in gliomas, the expression level of CCAAT enhancer-binding protein alpha in samples with 1p/19q codeletion was significantly decreased, which led to the downregulation of the immune checkpoints Galectin-9 and TIM-3. These results were validated in three independent datasets. The t-SNE analysis showed that the loss of chromosome 19q was the main reason for the promotion of the antitumor immune response. IHC protein staining, in vitro and in vivo experiments verified the results of bioinformatics analysis. In gliomas, 1p/19q codeletion can promote the antitumor immune response by downregulating the expression levels of the immune checkpoint TIM-3 and its ligand Galectin-9.

Whole-Tumor Histogram Analysis of Multiple Diffusion Metrics for Glioma Genotyping.

Background The isocitrate dehydrogenase (IDH) genotype and 1p/19q codeletion status are key molecular markers included in glioma pathologic diagnosis. Advanced diffusion models provide additional microstructural information. Purpose To compare the diagnostic performance of histogram features of multiple diffusion metrics in predicting glioma IDH and 1p/19q genotyping. Materials and Methods In this prospective study, participants were enrolled from December 2018 to December 2020. Diffusion-weighted imaging was performed by using a spin-echo echo-planar imaging sequence with five b values (500, 1000, 1500, 2000, and 2500 sec/mm2) in 30 directions for every b value and one b value of 0. Diffusion metrics of diffusion-tensor imaging (DTI), diffusion-kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) were calculated, and their histogram features were analyzed in regions that included the entire tumor and peritumoral edema. Comparisons between groups were performed according to IDH genotype and 1p/19q codeletion status. Logistic regression analysis was used to predict the IDH and 1p/19q genotypes. Results A total of 215 participants (115 men, 100 women; mean age, 48 years ± 13 [standard deviation]) with grade II (n = 68), grade III (n = 35), and grade IV (n = 112) glioma were included. Among the DTI, DKI, NODDI, MAP, and total diffusion models, there were no significant differences in the areas under the receiver operating characteristic curve (AUCs) for predicting IDH mutations (AUC, 0.76, 0.82, 0.78, 0.81, and 0.82, respectively; P > .05) and 1p/19q codeletion in gliomas with IDH mutations (AUC, 0.83, 0.81, 0.82, 0.83, and 0.88, respectively; P > .05). A regression model with an R2 value of 0.84 was used for the Ki-67 labeling index and histogram features of the diffusion metrics. Conclusion Whole-tumor histogram analysis of multiple diffusion metrics is a promising approach for glioma isocitrate dehydrogenase and 1p/19q genotyping, and the performance of diffusion-tensor imaging is similar to that of advanced diffusion models. Clinical trial registration no. ChiCTR2100048119 © RSNA, 2021 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on December 14, 2021.

157 Sensitive and specific detection of 1p/19q codeletion in gliomas by next generation sequencing

utility. Recently, inhibitors of spindle-regulatory proteins have attracted considerable attention, and transforming acidic coiled-coil-3 (TACC3) is a spindle-regulatory protein overexpressed in many human cancers. We have developed a protein knockdown system to induce degradation of target proteins via the ubiquitin–proteasome system in cells with hybrid molecules named SNIPER (Specific and Non-genetic IAP-dependent Protein ERaser). In this study, we designed and synthesized novel SNIPER(TACC3)s that target TACC3 for degradation, and evaluated their activity in vitro. SNIPER(TACC3)s induce poly-ubiquitylation and proteasomal degradation of TACC3, and reduce the TACC3 protein level in cells. Mechanistic analysis indicated that the ubiquitin ligase APC/C mediates the SNIPER(TACC3)-induced degradation of TACC3. Cancer cells express larger amount of TACC3 than do normal fibroblasts, and SNIPER(TACC3) selectively induced cell death in cancer cells. These results suggest protein knockdown of TACC3 by SNIPER(TACC3) is a potential strategy to treat cancers overexpressing the TACC3 protein.

Alpha‐internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy

Although it has been demonstrated that the neuronal intermediate filament alpha-internexin (INA) is closely related to 1p19q codeletion in gliomas, its prognostic and predictive value has not yet been confirmed in a prospective trial. The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospective, randomized European Organization for Research and Treatment of Cancer (EORTC) 26951 trial of adjuvant procarbazine, lomustine, and vincristine (PCV) in patients with anaplastic oligodendroglial tumors (AOTs). INA immunohistochemistry expression in tumors from 92 patients who were included in the EORTC 26951 trial was analyzed independently by 2 observers and was correlated with relevant clinical characteristics, including progression-free survival (PFS) and overall survival (OS), and with molecular features, including 1p/19q codeletion, isocitrate dehydrogenase 1 and 2 gene (IDH1/IDH2) mutation, and O-6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status. INA expression was observed in 33 tumors and was strongly correlated with 1p/19q codeletion, IDH1 mutations, and MGMT promoter methylation. It was associated with significantly better PFS and OS independent of the treatment received. By using Cox proportional hazard modeling for OS with stepwise selection, INA expression, patient age, and performance status were identified as independent prognostic factors. The results indicated that INA expression may have an impact on the efficacy of combined radiotherapy plus PCV. In a homogeneously treated group of patients with grade III AOTs, INA expression had strong favorable prognostic significance for OS and may have predictive value for sensitivity to chemotherapy.