Brain Neoplasms ; classification ; genetics ; pathology ; Humans

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.
Brain Neoplasms/pathology ; Brain Neoplasms/genetics* ; Human ; Meningioma/pathology ; Meningioma/genetics* ; Mutation* ; Neoplasm Invasiveness ; Protein p53/genetics*

OBJECTIVEThis overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.

DATA SOURCESUsing the keyword terms "glioma" and "miRNA," we performed the literature search in PubMed, Ovid, and web.metstr.com databases from their inception to October 2014.

STUDY SELECTIONIn screening out the quality of the articles, factors such as clinical setting of the study, the size of clinical samples were taken into consideration. Animal studied for verification and reviews article were also included in our data collection.

RESULTSDespite many advance in miRNA for malignant glioma, further studies were still required to focus on the following aspects: (i) Improving the understanding about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.

CONCLUSIONSWe discussed the most promising miRNA, correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics

OBJECTIVETo establish malignant progression associated gene expression profiles in human brain glioma.

METHODSThe primary (WHO grade II), recurrent (WHO grade III) and re-recurrent (WHO grade IV) glioma specimens were sequentially collected from one single patient. Gene expression of different tumor specimens and normal brain tissue of the same patient was compared by microarrary techniques.

RESULTS197 differentially expressed genes with differential ratio > or = 3 were observed when compared with normal brain tissue. When the specimens (3 tumor, 1 normal brain) were paired with each other, 7 groups containing 489 genes (upregulated 193, downregulated 296) were observed. According to the descending frequency of the 109 genes with known function, they were the genes associated with development, metabolism, differentiation, signal transduction, DNA binding transcription, cellular receptor, immunity, ion-channel transportation, protein translation, cell backbone motion, stress, protooncogene and anti-oncogene and cell apoptosis, respectively.

CONCLUSIONFrom the 197 differentially expressed genes found in one glioma patient experiencing tumor malignant progression, 17 genes screened out by bioinformatics assay, may offer valuable information on molecular mechanisms on genesis and malignant progression of glioma.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Profiling ; Glioma ; genetics ; pathology ; Humans ; Oligonucleotide Array Sequence Analysis

Animals ; Brain Neoplasms ; genetics ; pathology ; Cell Differentiation ; Cell Transformation, Neoplastic ; genetics ; Glioma ; genetics ; pathology ; Humans ; Neoplastic Stem Cells ; pathology ; Neural Stem Cells ; pathology ; Neuroglia ; pathology ; Neurons ; pathology

Brain Neoplasms ; pathology ; physiopathology ; DNA Repair ; genetics ; Glioma ; pathology ; physiopathology ; Humans ; Statistics as Topic ; Targeted Gene Repair

OBJECTIVETo summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease.

DATA SOURCESData cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1-MET", and "clinical treatment".

STUDY SELECTIONArticles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed.

RESULTSThere is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches.

CONCLUSIONThis review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.

Brain Neoplasms ; genetics ; pathology ; Glioblastoma ; genetics ; pathology ; Humans ; Isocitrate Dehydrogenase ; genetics ; Mutation ; PTEN Phosphohydrolase ; genetics ; Receptor, Epidermal Growth Factor ; genetics ; Telomerase ; genetics

To evaluate the effect of wild-type p53 gene on the growth and radiotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251 cells. p53 gene expression in transfected cells was detected by RT-PCR, and the cell growth inhibition and apoptosis in the absence or presence of irradiation were assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene alone induced strong inhibitory effect on the growth of U251 cells (inhibition rate (IR), (79.60 +/- 5.69)%). The killing effect of irradiation alone on U251 cells was not strong (IR: (17.06 +/- 4.35)% (17.39 +/- 1.67)% (18.73 +/- 4.68)%) and increased with the irradiation doses (3, 6, 9 Gy). When combined treatment of wild-type p53 gene transfection and irradiation was used, the effect was significantly increased (IR:(80.60 +/- 5.35)%. (90.30 +/- 1.67)%, (91.30 +/- 2.01)%). The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38%. The rate induced by irradiation increased (4.61%, 4.84%, 5.40%) with the irradiation doses (3, 6, 9 Gy). The apoptosis rate was also significantly increased (17.80%, 20.03%, 22.34%) after combined treatment of p53 and irradiation with different doses (3, 6, 9 Gy). It is concluded that wild-type p53 gene and irradiation could result in synergistic inhibitory effect on the growth of human glioma cells.
Apoptosis/*radiation effects ; Brain Neoplasms/genetics ; Brain Neoplasms/*pathology ; Genes, p53/*radiation effects ; Glioma/genetics ; Glioma/*pathology ; Transfection ; Tumor Cells, Cultured

Objective: To investigate the clinicopathological features of pediatric diffuse midline glioma with H3K27 alteration and to analyze their relationship with prognosis. Methods: Forty-one cases of childhood diffuse midline glioma with H3K27 alteration were collected at Children's Hospital of Fudan University (39 cases) and Xi'an Children's Hospital (2 cases), from July 2016 to July 2020. The clinical manifestations, imaging data, histopathology, immunohistochemical phenotype and molecular genetics features, tumor size, site and histological grading were evaluated. Results: Among the 41 cases, 21 were males and 20 females, the age of onset was 3-14 years, the average and median age was 7.6 years and 7.0 years, respectively. The tumor sites were brain stem (n=36) and other locations (n=5). The clinical manifestations were dizziness, gait disturbance, and limb weakness, etc. The MRI features were variable. The histology varied from low-grade to high-grade glioma with neuron differentiation. Immunohistochemistry showed that the tumor cells expressed H3K27M, GFAP, and Olig2. Genetic study showed that 76% (16/21) of tumors had H3F3A gene mutation, mostly accompanied by TP53 (62%, 13/21) missense mutation; five tumors (24%, 5/21) had HIST1H3B gene mutation, accompanied by missense mutations in ACVR1 and PI3K pathway-related gene PIK3CA (4/5) and PIK3R1 (1/5) mutations. The prognosis was dismal with only one alive and others died. The average and median overall survival time was 7 months and 4 months, respectively. Cox multivariate regression analysis showed that age, tumor location, radiologically maximum tumor diameter, histologic grading, and surgical methods were not significantly associated with overall survival rate (P>0.05). Conclusions: Pediatric diffuse midline gliomas with H3K27 alteration have unique clinicopathological and genetic characteristics. The prognosis is poor. The tumor location and histopathologic grading are not related to prognosis. New specific drugs and comprehensive treatment are needed to improve the prognosis.
Adolescent ; Brain Neoplasms/genetics* ; Child ; Child, Preschool ; Female ; Glioma/pathology* ; Histones/genetics* ; Humans ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Prognosis

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
Animals ; Brain Neoplasms ; genetics ; pathology ; Breast Neoplasms ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics ; Multifactorial Inheritance ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Proteins ; genetics ; Neoplasm Staging ; Neoplasms ; genetics ; Transcription, Genetic ; Transcriptome ; Tumor Suppressor Proteins ; genetics