Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 16.006
Filter
1.
Neurosurg Focus ; 57(2): E13, 2024 08 01.
Article in English | MEDLINE | ID: mdl-39088855

ABSTRACT

OBJECTIVE: Pediatric pilocytic astrocytoma (PPA) requires prolonged follow-up after initial resection. The landscape of transitional care for PPA patients is not well characterized. The authors sought to examine the clinical course and transition to adult care for these patients to better characterize opportunities for improvement in long-term care. METHODS: Pediatric patients (younger than 18 years at diagnosis) who underwent biopsy or resection for PPA between May 2000 and November 2022 at the authors' large academic center were retrospectively reviewed. Patient demographics, tumor characteristics, recurrence, adjuvant therapies, and follow-up data were extracted from the electronic medical record via chart review. Charts of patients who were 18 years or older as of January 1, 2024, were reviewed for adult follow-up notes. RESULTS: The authors identified 315 patients who underwent biopsy or resection for PPA between May 2000 and November 2022. The most common tumor location was posterior fossa (59.7%), and gross-total resection (GTR) was achieved in 187 patients (59.4%). In patients with GTR, progression/recurrence occurred less frequently (8.6% vs 41.4%, p < 0.01) compared to patients with non-GTR. Among 177 patients found to be age-eligible for transition to adult care, the authors found that 31 (17.5%) successfully transitioned. The average age at transition from pediatric to adult care was 21.7 years, and the average age at last known adult follow-up was 25.0 years. The authors found that patients who transitioned to adult care were followed longer (12.5 vs 7.0 years, p < 0.01) and were diagnosed at an older age (12.1 vs 9.6 years, p < 0.01) than their untransitioned counterparts. CONCLUSIONS: The authors found that there was a low rate of successful transition from pediatric to adult care for PPA; 17.5% of age-eligible patients are now cared for by adult providers, whereas an additional 18.6% completed appropriate follow-up during childhood and did not require transition to adult care. These findings underscore opportunities for improvement in the pediatric-to-adult transition process for patients with PPA, particularly for those with non-GTR who were not followed for at least 10 years, during which the risk of disease progression is thought to be highest.


Subject(s)
Astrocytoma , Brain Neoplasms , Transitional Care , Humans , Astrocytoma/surgery , Astrocytoma/therapy , Male , Female , Child , Adolescent , Brain Neoplasms/surgery , Brain Neoplasms/therapy , Retrospective Studies , Child, Preschool , Young Adult , Neoplasm Recurrence, Local/surgery , Adult , Transition to Adult Care , Infant , Follow-Up Studies , Neurosurgical Procedures/methods
2.
Sci Rep ; 14(1): 17922, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095557

ABSTRACT

Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.


Subject(s)
Brain Neoplasms , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , MicroRNAs , Humans , MicroRNAs/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Child , Male , Female , Adolescent , Child, Preschool , Medulloblastoma/genetics , Medulloblastoma/pathology , Astrocytoma/genetics , Astrocytoma/pathology , Ependymoma/genetics , Infant
3.
PLoS One ; 19(7): e0307818, 2024.
Article in English | MEDLINE | ID: mdl-39058662

ABSTRACT

INTRODUCTION: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients. METHODS: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time. TRIAL REGISTRATION: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.


Subject(s)
Brain Neoplasms , Neoplasm Recurrence, Local , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Astrocytoma/drug therapy , Astrocytoma/pathology , Astrocytoma/diagnostic imaging , Organoids/drug effects , Organoids/pathology , Organoids/diagnostic imaging , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Grading
5.
Bull Exp Biol Med ; 177(1): 169-175, 2024 May.
Article in English | MEDLINE | ID: mdl-38960964

ABSTRACT

In order to obtain models of gliomas of varying degrees of malignancy, we performed morphological and molecular genetic study of a tissue strain of glioma 10-17-2 (Astrid-17) obtained by intracranial passaging of tumor fragments of chemically induced rat brain tumor, and a cell strain isolated from it. More or less pronounced changes in the expression levels of Mki67, Trp53, Vegfa, and Gfap genes in the tissue and cell strain of glioma 10-17-2 (Astrid-17) compared with intact brain tissue were shown. The tissue model of glioma 10-17-2 (Astrid-17) according to the studied characteristics shows features of grade 3-4 astrocytoma and the cellular model - grade 2-3 astrocytoma.


Subject(s)
Brain Neoplasms , Glial Fibrillary Acidic Protein , Glioma , Vascular Endothelial Growth Factor A , Animals , Rats , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Glioma/genetics , Glioma/pathology , Glioma/metabolism , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ki-67 Antigen/metabolism , Ki-67 Antigen/genetics , Male , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Brain/pathology , Brain/metabolism
6.
Cell Mol Neurobiol ; 44(1): 54, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969910

ABSTRACT

The extracellular matrix (ECM) is a dynamic set of molecules produced by the cellular component of normal and pathological tissues of the embryo and adult. ECM acts as critical regulator in various biological processes such as differentiation, cell proliferation, angiogenesis, and immune control. The most frequent primary brain tumors are gliomas and by far the majority are adult astrocytic tumors (AATs). The prognosis for patients with these neoplasms is poor and the treatments modestly improves survival. In the literature, there is a fair number of studies concerning the composition of the ECM in AATs, while the number of studies relating the composition of the ECM with the immune regulation is smaller. Circulating ECM proteins have emerged as a promising biomarker that reflect the general immune landscape of tumor microenvironment and may represent a useful tool in assessing disease activity. Given the importance it can have for therapeutic and prognostic purposes, the aim of our study is to summarize the biological properties of ECM components and their effects on the tumor microenvironment and to provide an overview of the interactions between major ECM proteins and immune cells in AATs. As the field of immunotherapy in glioma is quickly expanding, we retain that current data together with future studies on ECM organization and functions in glioma will provide important insights into the tuning of immunotherapeutic approaches.


Subject(s)
Astrocytoma , Extracellular Matrix , Tumor Microenvironment , Humans , Extracellular Matrix/metabolism , Tumor Microenvironment/immunology , Astrocytoma/pathology , Astrocytoma/metabolism , Astrocytoma/immunology , Brain Neoplasms/pathology , Brain Neoplasms/immunology , Brain Neoplasms/metabolism , Adult , Animals , Extracellular Matrix Proteins/metabolism
7.
Cancer Med ; 13(13): e7369, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38970209

ABSTRACT

BACKGROUND: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. METHODS: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. RESULTS: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). CONCLUSIONS: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.


Subject(s)
Astrocytoma , Magnetic Resonance Imaging , Mutation , Neoplasm Grading , World Health Organization , Humans , Astrocytoma/genetics , Astrocytoma/classification , Astrocytoma/pathology , Astrocytoma/diagnostic imaging , Male , Female , Retrospective Studies , Middle Aged , Adult , Magnetic Resonance Imaging/methods , Prognosis , Isocitrate Dehydrogenase/genetics , Central Nervous System Neoplasms/classification , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/pathology , Central Nervous System Neoplasms/diagnostic imaging , Aged , Young Adult , Brain Neoplasms/classification , Brain Neoplasms/genetics , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/mortality , Adolescent
8.
Acta Neuropathol ; 148(1): 5, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012509

ABSTRACT

In recent years, the classification of adult-type diffuse gliomas has undergone a revolution, wherein specific molecular features now represent defining diagnostic criteria of IDH-wild-type glioblastomas, IDH-mutant astrocytomas, and IDH-mutant 1p/19q-codeleted oligodendrogliomas. With the introduction of the 2021 WHO CNS classification, additional molecular alterations are now integrated into the grading of these tumors, given equal weight to traditional histologic features. However, there remains a great deal of heterogeneity in patient outcome even within these established tumor subclassifications that is unexplained by currently codified molecular alterations, particularly in the IDH-mutant astrocytoma category. There is also significant intercellular genetic and epigenetic heterogeneity and plasticity with resulting phenotypic heterogeneity, making these tumors remarkably adaptable and robust, and presenting a significant barrier to the design of effective therapeutics. Herein, we review the mechanisms and consequences of genetic and epigenetic instability, including chromosomal instability (CIN), microsatellite instability (MSI)/mismatch repair (MMR) deficits, and epigenetic instability, in the underlying biology, tumorigenesis, and progression of IDH-mutant astrocytomas. We also discuss the contribution of recent high-resolution transcriptomics studies toward defining tumor heterogeneity with single-cell resolution. While intratumoral heterogeneity is a well-known feature of diffuse gliomas, the contribution of these various processes has only recently been considered as a potential driver of tumor aggressiveness. CIN has an independent, adverse effect on patient survival, similar to the effect of histologic grade and homozygous CDKN2A deletion, while MMR mutation is only associated with poor overall survival in univariate analysis but is highly correlated with higher histologic/molecular grade and other aggressive features. These forms of genomic instability, which may significantly affect the natural progression of these tumors, response to therapy, and ultimately clinical outcome for patients, are potentially measurable features which could aid in diagnosis, grading, prognosis, and development of personalized therapeutics.


Subject(s)
Astrocytoma , Brain Neoplasms , Disease Progression , Epigenesis, Genetic , Isocitrate Dehydrogenase , Mutation , Humans , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Astrocytoma/genetics , Astrocytoma/pathology , Isocitrate Dehydrogenase/genetics , Mutation/genetics , Epigenesis, Genetic/genetics
9.
Neurosciences (Riyadh) ; 29(3): 168-176, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38981632

ABSTRACT

OBJECTIVES: To elucidate the relationship between DNA methylation profiling (DMP) and pathological diagnosis (PD) in pediatric glial and glioneuronal tumors with B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations, addressing their diagnostic challenges. METHODS: This retrospective study, conducted in Saudi Arabia, analyzed 47 cases from the Children's Brain Tumor Network online database using scanned images, next-generation sequencing data, and methylation profiles processed using the Heidelberg methylation brain tumor classifiers v12.5 and v12.8. The data was last access on 10 November 2023. RESULTS: The highest prevalence of BRAF mutations was observed in pilocytic astrocytoma and ganglioglioma. The DMP was consistent with PD in 23 cases, but discrepancies emerged in others, including diagnostic changes in diffuse leptomeningeal glioneuronal tumor and polymorphous low-grade neuroepithelial tumor of the young. A key inconsistency appeared between a pilocytic astrocytoma MC and a glioneuronal tumor PD. Two high-grade astrocytomas were misclassified as pleomorphic xanthoastrocytomas. Additionally, low variant allelic frequency in gangliogliomas likely contributed to misclassifications as control in 5 cases. CONCLUSION: This study emphasized the importance of integrating DMP with PD in diagnosing pediatric glial and glioneuronal tumors with BRAF mutations. Although DMP offers significant diagnostic insights, its limitations, particularly in cases with low tumor content, necessitate cautious interpretation, as well as its use as a complementary diagnostic tool, rather than a definitive method.


Subject(s)
Brain Neoplasms , DNA Methylation , Mutation , Proto-Oncogene Mas , Proto-Oncogene Proteins B-raf , Humans , Proto-Oncogene Proteins B-raf/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/diagnosis , Brain Neoplasms/diagnostic imaging , Child , Male , Female , DNA Methylation/genetics , Retrospective Studies , Child, Preschool , Ganglioglioma/genetics , Ganglioglioma/pathology , Ganglioglioma/diagnostic imaging , Adolescent , Glioma/genetics , Glioma/pathology , Glioma/diagnosis , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/diagnostic imaging , Astrocytoma/diagnosis , Infant , Saudi Arabia
10.
Technol Cancer Res Treat ; 23: 15330338241262483, 2024.
Article in English | MEDLINE | ID: mdl-39043042

ABSTRACT

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.


Subject(s)
Astrocytoma , Spinal Cord Neoplasms , Humans , Astrocytoma/genetics , Astrocytoma/therapy , Astrocytoma/diagnosis , Astrocytoma/pathology , Spinal Cord Neoplasms/therapy , Spinal Cord Neoplasms/genetics , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/pathology , Biomarkers, Tumor/genetics , Pathology, Molecular , DNA Methylation , Disease Management , Prognosis , Neoplasm Grading
11.
J Med Case Rep ; 18(1): 330, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39030575

ABSTRACT

BACKGROUND: Subependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation. CASE REPORT: We present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy. CONCLUSION: There is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation.


Subject(s)
Astrocytoma , Brain Neoplasms , Everolimus , Radiosurgery , Humans , Female , Astrocytoma/radiotherapy , Astrocytoma/surgery , Adult , Brain Neoplasms/radiotherapy , Everolimus/therapeutic use , Magnetic Resonance Imaging , Antineoplastic Agents/therapeutic use , Treatment Outcome , Kidney Neoplasms/radiotherapy , Kidney Neoplasms/pathology , Tuberous Sclerosis/complications
12.
Oncol Res ; 32(6): 1037-1045, 2024.
Article in English | MEDLINE | ID: mdl-38827324

ABSTRACT

Background: The dysregulation of Isocitrate dehydrogenase (IDH) and the subsequent production of 2-Hydroxyglutrate (2HG) may alter the expression of epigenetic proteins in Grade 4 astrocytoma. The interplay mechanism between IDH, O-6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation, and protein methyltransferase proteins-5 (PRMT5) activity, with tumor progression has never been described. Methods: A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors. Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis. Inter-cohort statistical significance was evaluated. Results: Both IDH-mutant WHO grade 4 astrocytomas (n = 22, 64.7%) and IDH-wildtype glioblastomas (n = 12, 35.3%) had upregulated PRMT5 gene expression except in one case. Out of the 22 IDH-mutant tumors, 10 (45.5%) tumors showed MGMT-promoter methylation and 12 (54.5%) tumors had unmethylated MGMT. All IDH-wildtype tumors had unmethylated MGMT. There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma (p-value = 0.006). Statistically significant differences in progression-free survival (PFS) were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide (TMZ) or TMZ plus other chemotherapies, regardless of their IDH or MGMT-methylation status (p-value=0.0014). Specifically, IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation, who received only TMZ, have exhibited longer PFS. Conclusions: The relationship between PRMT5, MGMT-promoter, and IDH is not tri-directional. However, accumulation of D2-hydroxyglutarate (2-HG), which partially activates 2-OG-dependent deoxygenase, may not affect their activities. In IDH-wildtype glioblastomas, the 2HG-2OG pathway is typically inactive, leading to PRMT5 upregulation. TMZ alone, compared to TMZ-plus, can increase PFS in upregulated PRMT5 tumors. Thus, using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.


Subject(s)
Astrocytoma , DNA Methylation , DNA Modification Methylases , DNA Repair Enzymes , Disease Progression , Isocitrate Dehydrogenase , Mutation , Promoter Regions, Genetic , Protein-Arginine N-Methyltransferases , Tumor Suppressor Proteins , Humans , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , DNA Modification Methylases/genetics , DNA Modification Methylases/metabolism , Isocitrate Dehydrogenase/genetics , Male , Female , Astrocytoma/genetics , Astrocytoma/pathology , Middle Aged , Adult , Retrospective Studies , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Neoplasm Grading , Aged , Temozolomide/therapeutic use , Temozolomide/pharmacology , Gene Expression Regulation, Neoplastic
13.
Spinal Cord Ser Cases ; 10(1): 43, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909041

ABSTRACT

INTRODUCTION: Pilocytic astrocytoma is a low-grade glioma more frequently seen in patients <20. It is pretty uncommon in the spinal cord. Rarely, astrocytoma may involve the most or total length of the spinal cord; in that case, they are called "holo-cord astrocytoma." In this case report, we are reporting the third holo-cord pilocytic astrocytoma in an adult patient and the first with an extension to the Magendie foramen. CASE PRESENTATION: We presented a 24-year-old woman with complaints of progressively worsening neck and back pain since one year ago. The patient's MRI showed a very large intradural and intramedullary cystic lesion with a solid component within the spinal cord extending from the medulla to the conus medullaris. Partial resection of the solid part of the cervical portion of the tumor was performed. Histopathological evaluation of the resected tumor segments was compatible with grade I pilocytic astrocytoma. After one year of follow-up, neck and back pain has reduced, and neurological functions have improved. CONCLUSION: Spinal cord pilocytic astrocytoma may present as a holo-cord tumor and can rarely extend to the intracranial fossa. Although this tumor does not arise from the central canal, in this case, it was extended through the Magendie foramen. Symptoms could be subtle despite extensive cord involvement. On MRI, this tumor presents as an intramedullary holo-cord cystic lesion intermixed with a solid component with a variable enhancement of the solid component.


Subject(s)
Astrocytoma , Magnetic Resonance Imaging , Spinal Cord Neoplasms , Humans , Astrocytoma/diagnostic imaging , Astrocytoma/surgery , Female , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery , Spinal Cord Neoplasms/diagnosis , Young Adult , Adult
14.
Genes (Basel) ; 15(6)2024 May 28.
Article in English | MEDLINE | ID: mdl-38927643

ABSTRACT

Azoospermia is a form of male infertility characterized by a complete lack of spermatozoa in the ejaculate. Sertoli cell-only syndrome (SCOS) is the most severe form of azoospermia, where no germ cells are found in the tubules. Recently, FANCM gene variants were reported as novel genetic causes of spermatogenic failure. At the same time, FANCM variants are known to be associated with cancer predisposition. We performed whole-exome sequencing on a male patient diagnosed with SCOS and a healthy father. Two compound heterozygous missense mutations in the FANCM gene were found in the patient, both being inherited from his parents. After the infertility assessment, the patient was diagnosed with diffuse astrocytoma. Immunohistochemical analyses in the testicular and tumor tissues of the patient and adequate controls showed, for the first time, not only the existence of a cytoplasmic and not nuclear pattern of FANCM in astrocytoma but also in non-mitotic neurons. In the testicular tissue of the SCOS patient, cytoplasmic anti-FANCM staining intensity appeared lower than in the control. Our case report raises a novel possibility that the infertile carriers of FANCM gene missense variants could also be prone to cancer development.


Subject(s)
Astrocytoma , Mutation, Missense , Sertoli Cell-Only Syndrome , Humans , Male , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/diagnosis , Sertoli Cell-Only Syndrome/genetics , Sertoli Cell-Only Syndrome/pathology , Adult , Exome Sequencing , DNA Helicases/genetics , Azoospermia/genetics , Azoospermia/pathology , Azoospermia/diagnosis
15.
Acta Neuropathol Commun ; 12(1): 95, 2024 06 14.
Article in English | MEDLINE | ID: mdl-38877600

ABSTRACT

MYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN), prompting a deeper investigation into potential novel oncogenic mechanisms. Analysing comprehensive genomics profiles of 236 "IDH-mutant 1p/19q non-co-deleted" lower-grade gliomas from The Cancer Genome Atlas, we identified somatic genomic alterations within the PMN. In tumours without PMN-alterations but with MYC-overexpression, genes correlated with MYC-overexpression were identified. Our analyses yielded that 86/236 of astrocytomas exhibited no PMN-alterations, a subset of 21/86 displaying relative MYC overexpression. Within this subset, we discovered 42 genes inversely correlated with relative MYC expression, all on 19q. Further analysis pinpointed a minimal common region at 19q13.43, encompassing 15 genes. The inverse correlations of these 15 genes with relative MYC overexpression were re-confirmed using independent scRNAseq data. Further, the micro-deleted astrocytoma subset displayed significantly higher genomic instability compared to WT cases, but lower instability compared to PMN-hit cases. This newly identified 19q micro-deletion represents a potential novel mechanism underlying MYC dysregulation in astrocytomas. Given the prominence of 19q loss in IDH-mutant gliomas, our findings bear significant implications for understanding gliomagenesis.


Subject(s)
Astrocytoma , Brain Neoplasms , Chromosome Deletion , Chromosomes, Human, Pair 19 , Isocitrate Dehydrogenase , Proto-Oncogene Proteins c-myc , Humans , Isocitrate Dehydrogenase/genetics , Astrocytoma/genetics , Astrocytoma/pathology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Chromosomes, Human, Pair 19/genetics , Mutation
17.
Neuroradiology ; 66(8): 1267-1277, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38834877

ABSTRACT

PURPOSE: The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values. METHODS: This retrospective study, spanning 2016-2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC. RESULTS: The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values. CONCLUSION: Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma's pure edema.


Subject(s)
Astrocytoma , Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Glioblastoma/surgery , Male , Astrocytoma/diagnostic imaging , Astrocytoma/surgery , Astrocytoma/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Female , Middle Aged , Retrospective Studies , Adult , Neoplasm Grading , Diagnosis, Differential , Magnetic Resonance Imaging/methods , Cerebral Blood Volume , Preoperative Care/methods
18.
Anticancer Res ; 44(7): 3005-3011, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38925840

ABSTRACT

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma. PATIENTS AND METHODS: A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on "brain lower grade glioma". mRNA expression rates were used to validate our findings on survival analysis. RESULTS: Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data. CONCLUSION: High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.


Subject(s)
Adaptor Proteins, Signal Transducing , Astrocytoma , Brain Neoplasms , Transcription Factors , YAP-Signaling Proteins , Humans , YAP-Signaling Proteins/metabolism , Astrocytoma/metabolism , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/mortality , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Female , Male , Transcription Factors/genetics , Transcription Factors/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Middle Aged , Adult , Neoplasm Grading , Oligodendroglioma/genetics , Oligodendroglioma/metabolism , Oligodendroglioma/pathology , Oligodendroglioma/mortality , Phosphoproteins/metabolism , Phosphoproteins/genetics , Aged , Prognosis , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Trans-Activators/genetics , Trans-Activators/metabolism , Young Adult
20.
In Vivo ; 38(4): 1671-1676, 2024.
Article in English | MEDLINE | ID: mdl-38936911

ABSTRACT

BACKGROUND/AIM: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing. CASE REPORT: Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions. CONCLUSION: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.


Subject(s)
Astrocytoma , Cyclin-Dependent Kinase Inhibitor p15 , Cyclin-Dependent Kinase Inhibitor p16 , Germ-Line Mutation , Humans , Cyclin-Dependent Kinase Inhibitor p16/genetics , Astrocytoma/genetics , Astrocytoma/pathology , Cyclin-Dependent Kinase Inhibitor p15/genetics , Germ-Line Mutation/genetics , High-Throughput Nucleotide Sequencing , Genetic Predisposition to Disease , Male , Female , Adult , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Pedigree , Magnetic Resonance Imaging , Gene Deletion
SELECTION OF CITATIONS
SEARCH DETAIL