A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas

Rème, Thierry; Hugnot, Jean‐Philippe; Bièche, Ivan; Rigau, Valérie; Burel‐Vandenbos, Fanny; Prévot, Vincent; Baroncini, Marc; Fontaine, Denys; Chevassus, Hugues; Vacher, Sophie; Lidereau, Rosette; Duffau, Hugues; Bauchet, Luc; Joubert, Dominique

doi:10.1371/journal.pone.0066574

Cited by 7 publications

(4 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 Grade II designates a low grade, whereas grade III represents a transition toward GBM, the most aggressive state. However, in practice, grades II and III cannot be easily distinguished, 36 which led us to compare pooled patient samples from grade II/III with those from GBM. tRNA i Met and tRNA e Met levels were increased in high-grade tumors (Figures 4a and b).…”

Section: Resultsmentioning

confidence: 99%

TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

et al. 2015

View full text Add to dashboard Cite

Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAi(Met)-overexpressing cells, PKCα overexpression decreased tRNAi(Met) expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.

show abstract

Section: Resultsmentioning

confidence: 99%

TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Furthermore, in a survey of the Cancer Genome Atlas Data Portal, increased expression of glypican‐6, agrin, serglycin and perlecan/HSPG2 was revealed . Specifically, the gene encoding perlecan/HSPG2 recently appeared in a pool of predictor genes for poor prognosis in high‐grade (grade III and IV) gliomas , which highlights its importance in glioma growth.…”

Section: Glioma‐associated Changes In the Ecm Include Alterations In mentioning

confidence: 99%

Heparan sulfate in the regulation of neural differentiation and glioma development

2014

View full text Add to dashboard Cite

Heparan sulfate proteoglycans (HSPGs) are the main components of the extracellular matrix, where they interact with a large number of physiologically important macromolecules. The sulfation pattern of heparan sulfate (HS) chains determines the interaction potential of the proteoglycans. Enzymes of the biosynthetic and degradation pathways for HS chains are thus important regulators in processes ranging from embryonic development to tissue homeostasis, but also for tumor development. Formation of the nervous system is also critically dependent on intact HSPGs, and several studies have outlined the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common malignant primary brain tumor among adults, and the outcome is poor. Neural stem cells and glioma stem cells have several common traits, such as sustained proliferation and a highly efficient migratory capacity in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside, and the tumorigenic niche. These include interactions with the extracellular matrix, and many of the matrix components are deregulated in glioma, e.g. HSPGs and enzymes implementing the biosynthesis and modification of HS. In this article, we will present how HS-regulated pathways are involved in neural differentiation, and discuss their impact on brain development. We will also review and critically discuss the important role of structural modifications of HS in glioma growth and invasion. We propose that targeting invasive mechanisms of glioma cells through modulation of HS structure and HS-mediated pathways may be an attractive alternative to other therapeutic attempts, which so far have only marginally increased survival for glioma patients.

show abstract

“…Resulting raw data was processed by the means of a bioinformatics pipeline dedicated to multivariate analysis of RNA marks. We applied this setting for analyzing a previously established cohort of adult diffuse glioma patients. , Glioma is the most common malignant tumor of the central nervous system, characterized by a significant variability in age of onset, histological and biological characteristics, and prognosis. It can be classified histologically according to the phenotype of tumoral cells: oligodendrogliomas and astrocytomas showing morphology reminiscent of oligodendrocyte and astrocyte lineage cells, respectively .…”

mentioning

confidence: 99%

Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics

et al. 2022

View full text Add to dashboard Cite

One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of “biomarker signatures” that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.e., genomics, transcriptomics, proteomics, metabolomics) but not from epitranscriptomics, which encompasses more than 100 biochemical modifications driving the post-transcriptional fate of RNA: stability, splicing, storage, and translation. We and others have studied chemical marks in isolation and associated them with cancer evolution, adaptation, as well as the response to conventional therapy. In this study, we have designed a unique pipeline combining multiplex analysis of the epitranscriptomic landscape by high-performance liquid chromatography coupled to tandem mass spectrometry with statistical multivariate analysis and machine learning approaches in order to identify biomarker signatures that could guide precision medicine and improve disease diagnosis. We applied this approach to analyze a cohort of adult diffuse glioma patients and demonstrate the existence of an “epitranscriptomics-based signature” that permits glioma grades to be discriminated and predicted with unmet accuracy. This study demonstrates that epitranscriptomics (co)evolves along cancer progression and opens new prospects in the field of omics molecular profiling and personalized medicine.

show abstract

A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas

Cited by 7 publications

References 59 publications

TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

Heparan sulfate in the regulation of neural differentiation and glioma development

Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics

Contact Info

Product

Resources

About