-
Brain Pathology (Zurich, Switzerland) Jan 2024The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to...
The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to codeletion of 1p/19q to characterize IDH-mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of CDKN2A/B and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 IDH-mutant gliomas (8 astrocytomas and 11 oligodendrogliomas) from patients. The whole-arm 1p/19q codeletion was detected in all oligodendrogliomas with high concordance among nCNV-seq, FISH, DNA methylation profiling, and whole-genome sequencing. For the CDKN2A/B deletion, nCNV-seq detected the loss in both astrocytoma and oligodendroglioma, with strong correlation with the CNV profiles derived from whole-genome sequencing (Pearson correlation (r) = 0.95, P < 2.2 × 10 to r = 0.99, P < 2.2 × 10 ) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of CDKN2A/B. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of IDH-mutant gliomas without capital expenditure for a sequencer.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Nanopore Sequencing; Mutation; Glioma; Astrocytoma; Isocitrate Dehydrogenase; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19
PubMed: 37574201
DOI: 10.1111/bpa.13203 -
Neuro-oncology Jan 2023Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower grade malignancy.... (Review)
Review
Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower grade malignancy. However, recent molecular profiling has identified specific aggressive tumor subgroups with clear clinical prognostic implications that are independent of histologic grading. The homozygous deletion of CDKN2A/B is the strongest implicated independent indicator of the poor prognosis within IDH-mutant astrocytoma, and the identification of this alteration in these lower histologic grade tumors transforms their biology toward an aggressive grade 4 phenotype clinically. CDKN2A/B homozygous deletion is now sufficient to define a grade 4 tumor in IDH-mutant astrocytomas regardless of histologic appearance, yet there are currently no effective molecularly informed targeted therapies for these tumors. The biological impact of CDKN2A/B homozygous deletion in IDH-mutant tumors and the optimal treatment strategy for this molecular subgroup remains insufficiently explored. Here we review the current understanding of the translational significance of homozygous deletion of CDKN2A/B gene expression in IDH-mutant astrocytoma and associated diagnostic and therapeutic implications.
Topics: Humans; Astrocytoma; Brain Neoplasms; Cyclin-Dependent Kinase Inhibitor p16; Homozygote; Isocitrate Dehydrogenase; Mutation; Sequence Deletion
PubMed: 35973817
DOI: 10.1093/neuonc/noac205 -
Turkish Neurosurgery 2022To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children.
AIM
To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children.
MATERIAL AND METHODS
Files (2006 to 2020) of children diagnosed with glial tumors and followed-up were reviewed retrospectively. Information regarding demographic and clinical characteristics, treatment approaches, and outcomes were retrieved from the patients? files.
RESULTS
Of the total of 180 pediatric patients diagnosed with brain tumors, 73 (40.6%) had glial tumors. The children with astrocytoma were in the age range of 2?18 years (median age: 8.7 years), while the ages of children with ependymoma ranged from three months to 10 years (median age: 3 years). This difference was statistically significant (p < 0.0001). The male to female ratio was 1.6. The most common symptoms or signs were headaches (n=34, 46.6%), abnormal gait or coordination (n=22, 30.2%), vomiting (n=21, 28.8%), and cranial nerve palsies (n=20, 27.4%). The pathological diagnoses were astrocytomas (n=53, 72.6%), oligodendroglial tumors (n=2, 2.7%), ependymoma (n=15, 20.7%), and other glial tumors (n=3, 4.1%). The most common tumor location was supratentorial (n=42, 57.5%), while midline glioma was detected in seven patients. The 5-year overall survival (OS) rate of all glial tumors, astrocytoma, and ependymoma was 42%, 40%, and 55%, respectively. The 5-year OS rate of the tumor Grade I, II, III, and IV was 77.2%, 45%, 32%, and 0%, respectively (p < 0.0001). The 5-year OS rate of supratentorial, infratentorial, and spinal tumors was 25.6%, 63.6%, and 50%, respectively (p=0.021). In Cox regression analysis, it was found that the tumor resection and grade had an effect on the tumor prognosis.
CONCLUSION
Treatment results are not satisfactory in high-grade astrocytomas. There is a need for new treatment approaches that would take cognizance of molecular features and adopt multidisciplinary approaches.
Topics: Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Female; Glioma; Humans; Infant; Male; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 34751424
DOI: 10.5137/1019-5149.JTN.34801-21.2 -
International Journal of Molecular... Dec 2022Glioblastoma (GB) is a primary malignancy of the central nervous system that is classified by the WHO as a grade IV astrocytoma. Despite decades of research, several... (Review)
Review
Glioblastoma (GB) is a primary malignancy of the central nervous system that is classified by the WHO as a grade IV astrocytoma. Despite decades of research, several aspects about the biology of GB are still unclear. Its pathogenesis and resistance mechanisms are poorly understood, and methods to optimize patient diagnosis and prognosis remain a bottle neck owing to the heterogeneity of the malignancy. The field of omics has recently gained traction, as it can aid in understanding the dynamic spatiotemporal regulatory network of enzymes and metabolites that allows cancer cells to adjust to their surroundings to promote tumor development. In combination with other omics techniques, proteomic and metabolomic investigations, which are a potent means for examining a variety of metabolic enzymes as well as intermediate metabolites, might offer crucial information in this area. Therefore, this review intends to stress the major contribution these tools have made in GB clinical and preclinical research and highlights the crucial impacts made by the integrative "omics" approach in reducing some of the therapeutic challenges associated with GB research and treatment. Thus, our study can purvey the use of these powerful tools in research by serving as a hub that particularly summarizes studies employing metabolomics and proteomics in the realm of GB diagnosis, treatment, and prognosis.
Topics: Humans; Proteomics; Glioblastoma; Metabolomics; Astrocytoma
PubMed: 36613792
DOI: 10.3390/ijms24010348 -
Oncogene Apr 2021Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been...
Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been unclear whether adult PAs arise early in life and remain asymptomatic until adulthood, or whether they develop during adulthood. We sought to determine the age and origin of adult human PAs using two types of "marks" in the genomic DNA. First, we analyzed the DNA methylation patterns of adult and pediatric PAs to distinguish between PAs of different anatomic locations (n = 257 PA and control brain tissues). Second, we measured the concentration of nuclear bomb test-derived C in genomic DNA (n = 14 cases), which indicates the time point of the formation of human cell populations. Our data suggest that adult and pediatric PAs developing in the infratentorial brain are closely related and potentially develop from precursor cells early in life, whereas supratentorial PAs might show age and location-specific differences.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Astrocytoma; Child; Child, Preschool; Humans; Incidence; Infant; Infant, Newborn; Middle Aged; Young Adult
PubMed: 33731860
DOI: 10.1038/s41388-021-01738-0 -
Neurosurgical Review Oct 2022The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the... (Review)
Review
The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the treatment spectrum of neuroendoscopy. This review aimed to present a systematic overview of the extent of resection, lesion characteristics, technical aspects, complications, and clinical outcomes related to using the NUA. Articles were identified by searching the PubMed/Medline, Embase, and Web of Science database through June 2022 with restriction to the last 20 years. We included case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews written in English. Studies reporting on endonasal approach or hematoma evacuation using the NUA were excluded. The references of the identified studies were reviewed as well. Nine full-text articles were included in the analysis, with a total of 40 patients who underwent surgery for a brain tumor using NUA. The most common underlying pathology treated by NUA was colloid cyst (17.5%), pilocytic astrocytoma (12.5%), subependymal giant cell astrocytoma (7.5%), subependymoma (7.5%), and craniopharyngioma (7.5%). Complete or near-total resection was achieved in 62.5%. The most frequently reported postoperative complication was secondary hydrocephalus (10%), meningitis/-encephalitis (7.5%), cognitive impairment (7.5%), and subdural hygroma (7.5%). In one case (2.5%), surgery-related death occurred due to a severe course of meningoencephalitis. According to the preliminary data, NUA seems to be a safe and efficient minimally invasive alternative to conventional microscopic resection of brain tumors. Further studies to investigate advantages and disadvantages of using the NUA are needed.
Topics: Astrocytoma; Brain; Brain Neoplasms; Colloid Cysts; Humans; Neuroendoscopy; Pituitary Neoplasms; Ultrasonics
PubMed: 35896917
DOI: 10.1007/s10143-022-01837-w -
Spinal Cord Series and Cases Nov 2021Gliofibroma is a rare tumor that develops in the brain and spinal cord. Due to the rarity of its nature, its pathophysiology and appropriate treatment remain elusive. We...
INTRODUCTION
Gliofibroma is a rare tumor that develops in the brain and spinal cord. Due to the rarity of its nature, its pathophysiology and appropriate treatment remain elusive. We report a case of intramedullary spinal cord gliofibroma that was surgically treated multiple times. This report is of great significance because this is the first case of recurrence of this tumor.
CASE PRESENTATION
A 32-year-old woman complained of gait disturbance and was referred to our institution. At the age of 13 years, she was diagnosed with intramedullary gliofibroma and underwent gross total resection (GTR) in another hospital. Based on imaging findings, tumor recurrence was suspected at the level of cervical spinal cord, and surgery was performed. However, the resection volume was limited to 50% because the boundary between the tumor and spinal cord tissue was unclear and intraoperative neuromonitoring alerted paralysis. At 1 year postoperatively, the second surgery was performed to try to resect the residual tumor, but subtotal resection was achieved at most. At 2 years after the final surgery, no tumor recurrence was observed, and neurologic function was maintained to gait with cane.
DISCUSSION
Although complete resection is desirable for this rare tumor at the initial surgery, there is a possibility to recur even after GTR with long-term follow-up. During surgical treatment for tumor recurrence, fair adhesion to the spinal cord is expected, and reoperation and/or adjuvant therapy might be considered in the future if the tumor regrows and triggers neurological deterioration.
Topics: Adolescent; Adult; Astrocytoma; Female; Humans; Neurosurgical Procedures; Spinal Cord Neoplasms; Treatment Outcome
PubMed: 34741004
DOI: 10.1038/s41394-021-00461-y -
Archives of Pathology & Laboratory... Aug 2023Glioma is the most common primary brain tumor in adults. The diagnosis and grading of different pathological subtypes of glioma is essential in treatment planning and...
CONTEXT.—
Glioma is the most common primary brain tumor in adults. The diagnosis and grading of different pathological subtypes of glioma is essential in treatment planning and prognosis.
OBJECTIVE.—
To propose a deep learning-based approach for the automated classification of glioma histopathology images. Two classification methods, the ensemble method based on 2 binary classifiers and the multiclass method using a single multiclass classifier, were implemented to classify glioma images into astrocytoma, oligodendroglioma, and glioblastoma, according to the 5th edition of the World Health Organization classification of central nervous system tumors, published in 2021.
DESIGN.—
We tested 2 different deep neural network architectures (VGG19 and ResNet50) and extensively validated the proposed approach based on The Cancer Genome Atlas data set (n = 700). We also studied the effects of stain normalization and data augmentation on the glioma classification task.
RESULTS.—
With the binary classifiers, our model could distinguish astrocytoma and oligodendroglioma (combined) from glioblastoma with an accuracy of 0.917 (area under the curve [AUC] = 0.976) and astrocytoma from oligodendroglioma (accuracy = 0.821, AUC = 0.865). The multiclass method (accuracy = 0.861, AUC = 0.961) outperformed the ensemble method (accuracy = 0.847, AUC = 0.933) with the best performance displayed by the ResNet50 architecture.
CONCLUSIONS.—
With the high performance of our model (>80%), the proposed method can assist pathologists and physicians to support examination and differential diagnosis of glioma histopathology images, with the aim to expedite personalized medical care.
Topics: Adult; Humans; Artificial Intelligence; Glioblastoma; Oligodendroglioma; Brain Neoplasms; Glioma; Astrocytoma
PubMed: 36445697
DOI: 10.5858/arpa.2021-0518-OA -
Cells Sep 2020Human astrocytic tumors are primary central nervous system (CNS) tumors that arise either from astrocytes or from precursor cells. A growing number of epidemiological...
Human astrocytic tumors are primary central nervous system (CNS) tumors that arise either from astrocytes or from precursor cells. A growing number of epidemiological and incidence studies in different countries underlined that, in addition to increasing economic costs for health systems, these cancers are still representing one of the main hurdles in developing a successful therapeutic goal for patients. On the other hand, new-omics technologies are offering customized instruments and more and more advantageous results toward personalized medicine approaches, underlining the concept that each tumor mass undergoes a peculiar transformation process under the control of specific genes' and proteins' functional signatures. The main aim of this Special Issue was to collect novel contributions in the wide field of human tumor astrocytic basic and translational research, to suggest further potential therapeutic targets/strategies that might interfere, possibly at the earliest stage of transformation, with the tumor progression, and to increase the molecular-based arsenal to counteract the prognostic poverty of high-grade astrocytic tumors.
Topics: Apoptosis; Astrocytoma; Brain Neoplasms; Genetic Therapy; Humans
PubMed: 33007988
DOI: 10.3390/cells9102216 -
Medicine Jun 2023The ubiquitin-proteasome pathway controls the monitoring and degradation of important proteins and is involved in several cellular processes, such as development,...
BACKGROUND
The ubiquitin-proteasome pathway controls the monitoring and degradation of important proteins and is involved in several cellular processes, such as development, differentiation, and transcriptional regulation. Recent evidence has shown that ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), a member of the deubiquitinating enzyme family that removes ubiquitin from protein substrates, is overexpressed in many types of cancer.
AIM
This study thus examined the expression of UCH-L1 in human astrocytoma tissues.
MATERIAL AND METHODS
Formalin-fixed, paraffin-embedded astrocytoma samples were obtained from 40 patients, after which histopathological examination, typing, and grading were performed. The study group included 10 histologically normal brain tissues, which served as the control group, and 10 WHO grade II, 10 WHO grade III, and 10 WHO grade IV (glioblastoma) samples. Normal brain tissue samples were obtained from the histologically normal, non-tumoral portion of the pathology specimens. UCH-L1 expression was evaluated using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.
RESULTS
Astrocytoma tissues exhibited higher UCH-L1 expression compared to the control group. UCH-L1 overexpression increased significantly together with the increase in astrocytoma grades (from II to IV).
CONCLUSION
UCH-L1 could be a good diagnostic and therapeutic marker for determining astrocytoma development and progression.
Topics: Humans; Ubiquitin Thiolesterase; Astrocytoma; Glioblastoma; Brain; Ubiquitin
PubMed: 37390278
DOI: 10.1097/MD.0000000000034132