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Nature Reviews. Clinical Oncology Jul 2017Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These... (Review)
Review
Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.
Topics: Central Nervous System Neoplasms; Glioma; Humans; Molecular Biology; Practice Guidelines as Topic; World Health Organization
PubMed: 28031556
DOI: 10.1038/nrclinonc.2016.204 -
Nature Aug 2019Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of... (Comparative Study)
Comparative Study
Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.
Topics: Animals; Cerebellar Neoplasms; Cerebellum; Child; Evolution, Molecular; Female; Fetus; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Glioma; Humans; Medulloblastoma; Mice; Sequence Analysis, RNA; Single-Cell Analysis; Time Factors; Transcription, Genetic; Transcriptome
PubMed: 31043743
DOI: 10.1038/s41586-019-1158-7 -
Theranostics 2022Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) involved in the regulation of the immune system and displayed a cell-type-specific pattern in...
Machine learning-based identification of tumor-infiltrating immune cell-associated lncRNAs for improving outcomes and immunotherapy responses in patients with low-grade glioma.
Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) involved in the regulation of the immune system and displayed a cell-type-specific pattern in immune cell subsets. Given the vital role of tumor-infiltrating lymphocytes in effective immunotherapy, we explored the tumor-infiltrating immune cell-associated lncRNA (TIIClncRNA) in low-grade glioma (LGG), which has never been uncovered yet. This study utilized a novel computational framework and 10 machine learning algorithms (101 combinations) to screen out TIIClncRNAs by integratively analyzing the sequencing data of purified immune cells, LGG cell lines, and bulk LGG tissues. The established TIIClnc signature based on the 16 most potent TIIClncRNAs could predict outcomes in public datasets and the Xiangya in-house dataset with decent efficiency and showed better performance when compared with 95 published signatures. The TIIClnc signature was strongly correlated to immune characteristics, including microsatellite instability, tumor mutation burden, and interferon γ, and exhibited a more active immunologic process. Furthermore, the TIIClnc signature predicted superior immunotherapy response in multiple datasets across cancer types. Notably, the positive correlation between the TIIClnc signature and CD8, PD-1, and PD-L1 was verified in the Xiangya in-house dataset. The TIIClnc signature enabled a more precise selection of the LGG population who were potential beneficiaries of immunotherapy.
Topics: Glioma; Humans; Immunologic Factors; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Machine Learning; RNA, Long Noncoding
PubMed: 35966587
DOI: 10.7150/thno.74281 -
BioMed Research International 2014
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Signal Transduction
PubMed: 25243142
DOI: 10.1155/2014/470523 -
CNS Neuroscience & Therapeutics Aug 2023Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative... (Review)
Review
Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative combined chemo- and radio-therapy, are ineffective in improving patients' long-term survival. The tumor microenvironment (TME) consists of stromal cells, tumor components, and innate and acquired immune cells, and these cells, along with the extracellular matrix, regulate and communicate intercellularly to promote TME formation. The immune microenvironment plays a vital role in the development of glioma. Exosomes, which are extracellular vesicles (EVs), facilitate intercellular communication and regulation within the TME. Tumor cells can release exosomes to transmit messages, induce macrophage polarization, and inhibit immune cell activity, ultimately promoting metastasis and immune evasion. Moreover, immune cells can regulate tumorigenesis and progression through exosomes. This review summarized the biological properties of exosomes and their effects on the tumor microenvironment and provides an overview of the interactions between glioma cells and immune cells.
Topics: Humans; Exosomes; Tumor Microenvironment; Glioma; Extracellular Vesicles; Cell Communication; Neoplasms
PubMed: 37170647
DOI: 10.1111/cns.14239 -
The Oncologist Apr 2014Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with... (Review)
Review
Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer-term survival in comparison with high-grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment-related risks. We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated.
Topics: Adult; Brain Neoplasms; Glioma; Humans; Radiography; Treatment Outcome; Young Adult
PubMed: 24664484
DOI: 10.1634/theoncologist.2013-0345 -
Neurology India 2020Are we witnessing the end of the biopsy as we know it? Is this the start of a revolution in cancer diagnostics and treatment where analysis of somatic mutations present... (Review)
Review
BACKGROUND
Are we witnessing the end of the biopsy as we know it? Is this the start of a revolution in cancer diagnostics and treatment where analysis of somatic mutations present in the blood, CSF, or urine followed by targeted therapy replaces the traditional surgery followed by chemo-radiation? Since 2016, molecular markers are an integral part of the 'glioma' treatment decision-making process- diagnostic, prognostic, and therapeutic. A lot of these somatic mutations that identify and prognosticate tumors are also detected in the adjoining bio-fluids in serum or CSF- the sampling of which is known as liquid biopsy.
OBJECTIVE
The objective of this study is to review the advancement of scientific techniques that now allows the investigation of these bio-fluids, to diagnose, prognosticate and treat gliomas.
MATERIAL AND METHODS
This review article is an exhaustive review of the literature that summarises the role of the three main liquid biopsy modalities- Circulating Tumor Cells, Cell-free Tumor DNA and Exosomes in the detection of known diagnostic and prognostic markers in gliomas.
RESULTS
The current review highlights the strengths and weaknesses of the diffrerent modalities in use, and their potential use in the clinical setting.
CONCLUSION
Liquid biopsies hold tremendous potential in the diagnosis and management of gliomas in the future.
Topics: Biomarkers, Tumor; Glioma; Humans; Liquid Biopsy; Neoplastic Cells, Circulating; Prognosis
PubMed: 33342856
DOI: 10.4103/0028-3886.304105 -
Frontiers in Immunology 2023Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory...
INTRODUCTION
Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.
METHODS
In the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.
RESULTS
TMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.
DISCUSSION
Taken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.
Topics: Humans; Astrocytoma; Epithelial-Mesenchymal Transition; Glioma; Prognosis; Transcriptome
PubMed: 37261362
DOI: 10.3389/fimmu.2023.1173518 -
CNS Oncology Jan 2018High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases,... (Review)
Review
High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.
Topics: Brain Neoplasms; Disease Management; Glioma; Humans; Neoplasm Grading
PubMed: 29241354
DOI: 10.2217/cns-2017-0026 -
Cancer Dec 2017The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with... (Review)
Review
The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms. Herein, the authors discuss the discovery of IDH mutations and associated molecular alterations in glioma, review clinical features common to patients with IDH-mutant glioma, and highlight current understanding of IDH mutation-driven gliomagenesis with implications for emerging treatment strategies. Cancer 2017;123:4535-4546. © 2017 American Cancer Society.
Topics: Glioma; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 28980701
DOI: 10.1002/cncr.31039