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Neuro-oncology Jul 2020
Topics: Adult; Biomarkers; Brain Neoplasms; Humans; Oligodendroglioma
PubMed: 32296823
DOI: 10.1093/neuonc/noaa097 -
Molecular Medicine (Cambridge, Mass.) Mar 2022IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the...
BACKGROUND
IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the molecular differences between IDH-mutant astrocytoma and oligodendroglioma grade 2. Therefore, we investigated the multiomics and clinical data regarding these two types of tumors.
METHOD
In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves.
RESULTS
Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma.
CONCLUSION
This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.
Topics: Astrocytoma; Brain Neoplasms; Chromosome Deletion; Genomics; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma; Tumor Microenvironment
PubMed: 35287567
DOI: 10.1186/s10020-022-00454-z -
Molecular and Clinical Oncology Aug 2021The present study aimed to evaluate the impact caused by the 2016 World Health Organization (WHO) diagnostic classification of gliomas in 139 patients studied in...
The present study aimed to evaluate the impact caused by the 2016 World Health Organization (WHO) diagnostic classification of gliomas in 139 patients studied in Argentina. Formalin-fixed paraffin-embedded tissues were used for histological and immunohistochemical analysis [glial fibrillary acidic protein, KI67, synaptophysin and isocitrate dehydrogenase (IDH)1-R132H]. DNA from formalin-fixed paraffin-embedded tissues was used for molecular analysis: 1p/19q co-deletion and mutation status of the IDH gene. These experiments were performed by direct Sanger sequencing and multiplex ligation-dependent probe amplification. According to the new classification, diagnoses included oligodendroglioma IDH-mutant and 1p/19q co-deletion (4.20%), anaplastic oligodendroglioma IDH-mutant and 1p/19q co-deletion (2.52%), diffuse astrocytoma IDH-mutant (6.72%), diffuse astrocytoma IDH-wild type (1.68%), anaplastic astrocytoma IDH-mutant (5.04%), anaplastic astrocytoma IDH-wild type (8.40%), glioblastoma IDH-mutant (5.88%) and glioblastoma IDH-wild type (65.56%). Regarding tumor histology, 60% of oligodendrogliomas, 35% of astrocytoma and 100% of unclassified gliomas were re-classified, while glioblastomas maintained their initial classification. Additionally, the present study evaluated the prognostic value of the histological grade for the 2007 and 2016 WHO classifications of gliomas. The histological subgroup associated with longer overall survival (OS) was grade II glioma (OS-2007WHO, 35.6 months; and OS-2016WHO, 47.7 months). Glioblastoma was the subgroup associated with a poor outcome (OS-2007WHO, 10.4 months; and OS-2016WHO, 11.1 months). The present study evaluated the OS of tumor grade subgroups with respect to their IDH status. For all subgroups, IDH-mutant tumors were associated with an improved prognosis compared with IDH-wild type tumors. The results suggested that the incorporation of molecular biomarkers in the new WHO classification improves tumor characterization and prognostic value of the subgroups.
PubMed: 34141429
DOI: 10.3892/mco.2021.2312 -
International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456 -
Asian Journal of Neurosurgery 2021Genetic subsets of oligodendrogliomas (OD) have distinct chromosomal and biophysical profiles. Pretherapeutic tumor grade and genotype analysis is a challenging aspect...
BACKGROUND
Genetic subsets of oligodendrogliomas (OD) have distinct chromosomal and biophysical profiles. Pretherapeutic tumor grade and genotype analysis is a challenging aspect of management, with 1p/19q codeletion status and grade of oligodendroglioma among the most important considerations for clinical decision making.
METHODOLOGY
Seventy-three patients with histopathological diagnosis of oligodendroglioma were selected, and their preoperative 1.5T magnetic resonance imaging (MRI) scans were reviewed through parameters including diffusion weighted image, susceptibility-weighted imaging, and apparent diffusion coefficient (ADC). These images were correlated with patients' histopathological and chromosomal testing. Tumor border irregularity, homogeneity, contrast enhancement, and other MRI characteristics were also studied. For analysis, descriptive statistics were generated, and normality was evaluated for ADC value, age, and Ki-67 tumor proliferation index.
OBJECTIVES
The study aimed to determine the correlation of ADC with Ki-67, grade, and 1p/19q co-deletion in oligodendroglioma at a tertiary care hospital within a low-middle income country.
RESULTS
Ki-67 tumor proliferation index was high in 33 tumors. It was found to be statistically significant ( = 0.048) with respect to ADC, showing that 1p/19q co-deleted tumors have a difference in their Ki-67 index. Ki-67 also showed a significant relationship ( < 0.05) with grade of OD. However, there was no statistically significant relationship between 1p19q chromosomal co-deletion and ADC. Linear regression was carried out as the data set was continuous. Univariate analysis showed no significant result with all values above 0.10.
CONCLUSION
Mean ADC is a viable tool to predict Ki-67 and assist prognostic clinical decisions. However, mean ADC alone cannot predict 1p/19q codeletion and tumor grades in OD. Further supplementation with other radiological modalities may provide greater yield and positive results.
PubMed: 35071073
DOI: 10.4103/ajns.AJNS_520_20 -
Cancer Biology & Medicine Nov 2022IDH-mutant lower-grade gliomas (LGGs, grade 2 or 3) eventually transform into secondary grade 4 astrocytomas (sA). Here, we sought to describe the transformation time,...
OBJECTIVE
IDH-mutant lower-grade gliomas (LGGs, grade 2 or 3) eventually transform into secondary grade 4 astrocytomas (sA). Here, we sought to describe the transformation time, risk factors, and outcomes in malignant transformation of IDH-mutant LGGs.
METHODS
We screened data for 108 patients with sA in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005-2021. We evaluated the transformation time from IDH-mutant LGGs to sA, and associated risk factors and outcomes. Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.
RESULTS
The median age of the 108 patients with IDH-mutant LGGs was 35 years (range, 19-54); the median age at transformation was 40 years (range, 25-62); and the median follow-up time for all patients was 146 months (range, 121-171). The average transformation time was 58.8 months for all patients with LGGs (range, 5.9-208.1); 63.5 and 51.9 months for grade 2 and 3 gliomas, respectively; and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas, respectively. Univariate and multivariate analysis indicated that radiotherapy [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.137-0.595; = 0.001] and non-A blood type (HR, 0.37; 95% CI, 0.203-0.680; = 0.001) were protective factors against delayed malignant transformation. Radiotherapy was associated with improved survival after transformation (HR, 0.44; 95% CI, 0.241-0.803; = 0.008), overall survival (HR, 0.50; 95% CI, 0.265-0.972; = 0.041), and progression-free survival (HR, 0.25; 95% CI, 0.133-0.479; < 0.0001) in patients with IDH-mutant gliomas.
CONCLUSIONS
Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDH-mutant gliomas.
Topics: Humans; Young Adult; Adult; Middle Aged; Isocitrate Dehydrogenase; Brain Neoplasms; Glioma; Oligodendroglioma; Astrocytoma; Glioblastoma; Cell Transformation, Neoplastic
PubMed: 36350001
DOI: 10.20892/j.issn.2095-3941.2022.0472 -
Cancers Jun 2020Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that participate in the regulation of pH homeostasis in addition to many other important physiological... (Review)
Review
Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that participate in the regulation of pH homeostasis in addition to many other important physiological functions. Importantly, CAs have been associated with neoplastic processes and cancer. Brain tumors represent a heterogeneous group of diseases with a frequently dismal prognosis, and new treatment options are urgently needed. In this review article, we summarize the previously published literature about CAs in brain tumors, especially on CA II and hypoxia-inducible CA IX and CA XII. We review here their role in tumorigenesis and potential value in predicting prognosis of brain tumors, including astrocytomas, oligodendrogliomas, ependymomas, medulloblastomas, meningiomas, and craniopharyngiomas. We also introduce both already completed and ongoing studies focusing on CA inhibition as a potential anti-cancer strategy.
PubMed: 32610540
DOI: 10.3390/cancers12071723 -
Brain Pathology (Zurich, Switzerland) Jul 2023The pathological diagnosis of intracranial germinoma (IG), oligodendroglioma, and low-grade astrocytoma on intraoperative frozen section (IFS) and hematoxylin-eosin...
The pathological diagnosis of intracranial germinoma (IG), oligodendroglioma, and low-grade astrocytoma on intraoperative frozen section (IFS) and hematoxylin-eosin (HE)-staining section directly determines patients' treatment options, but it is a difficult task for pathologists. We aimed to investigate whether whole-slide imaging (WSI)-based deep learning can contribute new precision to the diagnosis of IG, oligodendroglioma, and low-grade astrocytoma. Two types of WSIs (500 IFSs and 832 HE-staining sections) were collected from 379 patients at multiple medical centers. Patients at Center 1 were split into the training, testing, and internal validation sets (3:1:1), while the other centers were the external validation sets. First, we subdivided WSIs into small tiles and selected tissue tiles using a tissue tile selection model. Then a tile-level classification model was established, and the majority voting method was used to determine the final diagnoses. Color jitter was applied to the tiles so that the deep learning (DL) models could adapt to the variations in the staining. Last, we investigated the effectiveness of model assistance. The internal validation accuracies of the IFS and HE models were 93.9% and 95.3%, respectively. The external validation accuracies of the IFS and HE models were 82.0% and 76.9%, respectively. Furthermore, the IFS and HE models can predict Ki-67 positive cell areas with R of 0.81 and 0.86, respectively. With model assistance, the IFS and HE diagnosis accuracy of pathologists improved from 54.6%-69.7% and 53.5%-83.7% to 87.9%-93.9% and 86.0%-90.7%, respectively. Both the IFS model and the HE model can differentiate the three tumors, predict the expression of Ki-67, and improve the diagnostic accuracy of pathologists. The use of our model can assist clinicians in providing patients with optimal and timely treatment options.
Topics: Humans; Deep Learning; Oligodendroglioma; Ki-67 Antigen; Neuropathology; Brain Neoplasms; Astrocytoma
PubMed: 37186490
DOI: 10.1111/bpa.13160 -
Neuro-oncology Jul 2022With improved outcome following aggressive treatment in patients with grade 2 and 3 IDH-mutant (IDHmt), 1p/19q codeleted oligodendroglioma and IDHmt, non-codeleted... (Review)
Review
With improved outcome following aggressive treatment in patients with grade 2 and 3 IDH-mutant (IDHmt), 1p/19q codeleted oligodendroglioma and IDHmt, non-codeleted astrocytoma, prolonged surveillance is desirable for early detection of tumor growth and malignant transformation. Current National Comprehensive Cancer Network (NCCN) guidelines provide imaging follow-up recommendations based on molecular classification of lower-grade gliomas, although individualized imaging guidelines based on treatments received and after tumor recurrence are not clearly specified. Other available guidelines have yet to incorporate the molecular biomarkers that inform the WHO classification of gliomas, and in some cases do not adequately consider current knowledge on IDHmt glioma growth rate and recurrence patterns. Moreover, these guidelines also do not provide specific recommendations for concerning clinical symptoms or radiographic findings warranting imaging studies out of prespecified intervals. Focusing on molecularly defined grade 2 and 3 IDHmt astrocytomas and oligodendrogliomas, we review current knowledge of tumor growth rates and time to tumor progression for each tumor type and propose a range of recommended MRI surveillance intervals for both the newly diagnosed and recurrent tumor setting. Additionally, we summarize situations in which imaging is advisable outside of these intervals.
Topics: Adult; Astrocytoma; Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma; Retrospective Studies; World Health Organization
PubMed: 35137214
DOI: 10.1093/neuonc/noac031 -
The Journal of Veterinary Medical... Oct 2023An 11-year-old spayed female French bulldog was referred on suspicion of nasal tumor. Anaplastic oligodendroglioma in the olfactory bulb that was suspected to have...
An 11-year-old spayed female French bulldog was referred on suspicion of nasal tumor. Anaplastic oligodendroglioma in the olfactory bulb that was suspected to have invaded the nasal cavity was diagnosed from imaging and histopathology. Metastasis to cervical lymph nodes was suspected, with no other metastases identified. The brain-to-nasal lesion and lymph nodes were treated with hypo-fractionated radiation therapy. Nasal congestion soon resolved. About 3 months later, follow-up computed tomography revealed multiple hepatic and splenic masses, which were cytologically suspected as metastatic oligodendroglioma. Nimustine, followed by toceranib phosphate, seemed to have no effect, and the dog died on day 167. Postmortem examination revealed the primary tumor disappearance and systemic metastases. Canine oligodendroglioma can grow outside the cranial vault, and systemically metastasize.
Topics: Dogs; Animals; Female; Oligodendroglioma; Brain Neoplasms; Neck; Brain; Nose; Dog Diseases
PubMed: 37558495
DOI: 10.1292/jvms.23-0136