Materiały źródłowe

• #1 Oligodendroglioma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559184/

  Oligodendrogliomas (OGs) are primary brain tumors originating from oligodendrocytes, the glial cells responsible for myelination in the CNS. […] The hypothesis that OGs arise either from mature oligodendrocytes or neuroprogenitor cells with glial precursors, which differentiate into oligodendroglial-type cells lacking myelinating capabilities, is supported by shared driver mutations, particularly isocitrate dehydrogenase (IDH) mutations, which are common across various diffuse glioma subtypes and serve as early events in tumorigenesis. […] The etiology of OGs is multifactorial, involving genetic, environmental, epigenetic, and cellular factors. […] Genetically, the hallmark codeletion of chromosomal arms 1p and 19q is diagnostic in 70% to 90% of cases and correlates with better prognosis and therapy responsiveness.

• #2 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  OGs are primary brain tumors originating from oligodendrocytes, the glial cells responsible for myelination in the CNS. […] The hypothesis that OGs arise either from mature oligodendrocytes or neuroprogenitor cells with glial precursors, which differentiate into oligodendroglial-type cells lacking myelinating capabilities, is supported by shared driver mutations, particularly isocitrate dehydrogenase (IDH) mutations, which are common across various diffuse glioma subtypes and serve as early events in tumorigenesis. […] The etiology of OGs is multifactorial, involving genetic, environmental, epigenetic, and cellular factors. […] Genetically, the hallmark codeletion of chromosomal arms 1p and 19q is diagnostic in 70% to 90% of cases and correlates with better prognosis and therapy responsiveness.

• #3 Oligodendroglioma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Oligodendroglioma_pathophysiology

  Oligodendroglioma arises from the tripotential glial precursor cells and not from the bipotential oligodendrocytes. […] Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53, MGMT, TP73, BRAF, EGFR, and PTEN. […] Development of oligodendroglioma is the result of multiple genetic mutations. […] There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.

• #4

  https://www.advocatehealth.com/health-services/brain-spine-institute/brain-spine-tumors/oligodendroglioma

  Research shows that oligodendroglioma brain tumors dont start out as oligodendrocyte cells. Ongoing studies are searching for what kind of cells they grow from. […] We do know that they grow from a type of brain cell called a glial cell, so oligodendroglioma tumors fit into the category of glioma tumors along with astrocytomas and ependymomas. […] Research also shows that oligodendroglioma tumors start from different cells in adults than they do in children. […] Oligodendroglioma tumors are currently divided into two types. The type of cell is determined through biomarker testing of cancer cells and what the cells look like under a microscope. […] Part of the biopsied tissue will be used for biomarker testing to check for mutations or other changes in the genes in the cancer cells. The tests look for details about the cancer cells, including: Isocitrate dehydrogenase (IDH) mutation IDH is an enzyme found in cells

• #5 Oligodendroglioma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559184/

  Oligodendrogliomas (OGs) are primary brain tumors originating from oligodendrocytes, the glial cells responsible for myelination in the CNS. […] The hypothesis that OGs arise either from mature oligodendrocytes or neuroprogenitor cells with glial precursors, which differentiate into oligodendroglial-type cells lacking myelinating capabilities, is supported by shared driver mutations, particularly isocitrate dehydrogenase (IDH) mutations, which are common across various diffuse glioma subtypes and serve as early events in tumorigenesis. […] The etiology of OGs is multifactorial, involving genetic, environmental, epigenetic, and cellular factors. […] Genetically, the hallmark codeletion of chromosomal arms 1p and 19q is diagnostic in 70% to 90% of cases and correlates with better prognosis and therapy responsiveness.

• #6 Oligodendroglioma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Oligodendroglioma_pathophysiology

  Oligodendroglioma arises from the tripotential glial precursor cells and not from the bipotential oligodendrocytes. […] Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53, MGMT, TP73, BRAF, EGFR, and PTEN. […] Development of oligodendroglioma is the result of multiple genetic mutations. […] There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.

• #7

  https://journals.lww.com/neur/fulltext/2022/70030/clinical_profile,_pathology,_and_molecular_typing.29.aspx

  It is now essential to grade and type oligodendrogliomas by a combination of IDH, ATRX, and 1p19q deletion status to overcome the NOS category. […] A combined analysis of IDH, ATRX, and 1p19q codeletion has been emphasized and validated as an essential step in resolving the subtype of glioma to give the four-layered diagnosis. […] IDH mutations are present in 100% oligodendrogliomas. […] We observed that ATRX expression and codeletion were mutually exclusive similar to that given in literature. […] The presence of 1p19q codeletion is crucial to the tumors showing the morphology of oligodendroglioma with necrosis into anaplastic oligodendroglioma vs GBM-O. […] The study validates the integrated diagnosis of gliomas with the help of molecular genetics.

• #8 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazineccnuvincristine) chemotherapy, with virtually all tumors responding. […] In large prospective randomized studies on diffuse glioma, 1p/19q codeletion was associated with improved overall survival but also with increased benefit of adjuvant PCV chemotherapy given after radiotherapy. […] Following the initial discovery of isocitrate dehydrogenase (IDH) gene mutations in a small subset of especially younger glioblastoma patients with prolonged survival, a high percentage (70-80 %) of IDH1 and IDH2 mutations were identified in diffuse grade II and III gliomas, regardless of astrocytic or oligodendroglial cell type. […] Nearly all mutations involve codon 132 of IDH1 or the homologous codon 172 of IDH2, with c.395GA (p.R132H) representing 90 % of all IDH1 mutations. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100 %. […] Further studies have shown that IDH mutation is an early event in gliomagenesis (driver mutation), and likely precedes the development of the 1p/19q codeletion, the latter possibly specifically driving a diffuse glioma towards the classic oligodendroglioma morphologic phenotype, whereas superimposed TP53 and ATRX mutations drive it towards the astrocytoma phenotype instead.

• #9

  https://link.springer.com/article/10.1007/s00401-015-1424-1

  Through an altered substrate specificity, IDH mutations give rise to metabolic alterations, including an increase in production of 2-hydroxyglutarate (2-HG) which can inhibit histone demethylation and induces a glioma hypermethylation phenotype (glioma CpG island methylated phenotype or G-CIMP). […] In turn, this leads to a variety of downstream chromatin remodeling and transcriptional alterations. […] The presence of an IDH mutation may provide an opportunity to apply specific, IDH targeted treatment, no matter if the diagnosis was astrocytoma or (1p/19q codeleted) oligodendroglioma. […] This integrated diagnostic approach allows for much more robust recognition of biologically different subgroups within the spectrum of diffuse gliomas, thereby facilitating tailored treatment for individual patients.

• #10 Frontiers | Oligodendroglioma: A Review of Management and Pathways

  https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.722396/full

  IDH mutations identified in gliomas tend to occur at the active site of the enzyme at arginine 132 and 172 in IDH1 and IDH2, respectively. […] It was shown by Uhm (2010) that IDH mutations lead to the acquisition of a new enzymatic function that catalyzes the formation of D-2HG from alpha-KG. […] High mutant allele fractions have been found in patient samples at diagnosis and recurrence in tumor evolution studies. […] IDH mutated enzymes can promote proliferation and colony formation through its end metabolite 2-HG. […] The unbalanced translocation of the centromeric regions of chromosomes 1p and 19q attribute to the loss of the whole arm on both chromosomes. […] Following the stratification of AO according to 1p/19q co-deletion status, an in-depth genetic analysis of 1p/19q co-deleted tumors revealed inactivating mutations affecting the FUBP1 gene on chromosome 1p and the CIC gene on chromosome 19.

• #11 Oligodendroglioma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559184/

  Oligodendrogliomas (OGs) are primary brain tumors originating from oligodendrocytes, the glial cells responsible for myelination in the CNS. […] The hypothesis that OGs arise either from mature oligodendrocytes or neuroprogenitor cells with glial precursors, which differentiate into oligodendroglial-type cells lacking myelinating capabilities, is supported by shared driver mutations, particularly isocitrate dehydrogenase (IDH) mutations, which are common across various diffuse glioma subtypes and serve as early events in tumorigenesis. […] The etiology of OGs is multifactorial, involving genetic, environmental, epigenetic, and cellular factors. […] Genetically, the hallmark codeletion of chromosomal arms 1p and 19q is diagnostic in 70% to 90% of cases and correlates with better prognosis and therapy responsiveness.

• #12 Oligodendroglioma – Wikipedia

  https://en.wikipedia.org/wiki/Oligodendroglioma

  Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. […] The cause of oligodendrogliomas is unknown. Some studies have linked oligodendroglioma with a viral cause. A 2009 Oxford Neurosymposium study illustrated a 69% correlation between NJDS gene mutation and the tumor initiation. […] In the WHO 2021 CNS5 Classification, oligodendroglioma is named „Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted”, and requires the presence of IDH1 or IDH2 mutations and the codeletion of chromosome 1p and 19q arms. Interestingly, oligodendroglioma has a higher rate of IDH2 mutation than astrocytoma, so the IHC antibody against the common IDH1 p.R132H mutant might not pick up the mutation. […] By far, the most common structural deformity found is co-deletion of chromosomal arms 1p and 19q. The high frequency of co-deletion is a striking feature of this glial tumour and is considered as a „genetic signature” of oligodendroglioma.

• #13 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Like other neoplasms, diffuse gliomas develop as a result of genetic and molecular alterations that further accumulate with tumor progression. […] These aberrations allow the tumor to acquire assets for sustained survival and growth and to escape normal growth restraining influences. […] Some of these molecular abnormalities carry important diagnostic, prognostic and/or predictive information, giving support for a major molecular component in future tumor characterization. […] The most promising markers for oligodendroglial tumors are briefly discussed below. […] In 1994, using restriction fragment length polymorphism analysis, Reifenberger et al. reported for the first time that many oligodendroglial tumors show loss of heterozygosity (LOH) for chromosome arms 1p and 19q. […] Further studies have shown that 1p/19q loss in fact results from a non-balanced translocation t (1:19) (q10:p10) with subsequent loss of one of the derivative chromosomes. […] This explains why it is the loss of the entire arms of 1p and 19q that is related to clinical outcome, rather than smaller terminal or interstitial deletions which occur by a completely different mechanism and are occasionally encountered in astrocytic tumors, such as glioblastoma. […] Recently, by using genome-wide, 50 base pair single-end sequencing, 1p/19q codeletion was demonstrated to be the only copy number aberration that was stable across spatial regions of low-grade diffuse gliomas and their recurrences. […] Virtually all 1p/19q codeleted tumors have a pro-neural expression profile, supporting the hypothesis that these gliomas originate from a bi-potential progenitor cell able to give rise to neurons and oligodendrocytes.

• #14 Is Anaplastic Oligodendroglioma Prone to Extracranial Metastasis? A Case Report and Review of Literature

  https://www.mathewsopenaccess.com/full-text/is-anaplastic-oligodendroglioma-prone-to-extracranial-metastasis-a-case-report-and-review-of-literature

  The 1p/19q co-deletion is mediated by an unbalanced translocation of 19p to 1q:der (1;19) (p10;q10), which occurs during the tumorigenesis of oligodendroglioma. […] The prolonged survival resulting from concomitant radiotherapy and chemotherapy, which could significantly alter the immune status of patients with primary brain tumors, will probably increase the possibility of the development of undetected metastases. […] The R132H mutation combined with 1p/19q LOH may have led to a longer survival time under comprehensive therapy. The right pelvis metastasis had higher Ki67 than the original brain tumor, indicating that metastatic lesions might have more malignant potential than the original brain tumors after a long time survive. […] The relationship and mechanism of 1p19q LOH and IDH-1 mutation to extracranial metastasis requires further research in the future.

• #15 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Like other neoplasms, diffuse gliomas develop as a result of genetic and molecular alterations that further accumulate with tumor progression. […] These aberrations allow the tumor to acquire assets for sustained survival and growth and to escape normal growth restraining influences. […] Some of these molecular abnormalities carry important diagnostic, prognostic and/or predictive information, giving support for a major molecular component in future tumor characterization. […] The most promising markers for oligodendroglial tumors are briefly discussed below. […] In 1994, using restriction fragment length polymorphism analysis, Reifenberger et al. reported for the first time that many oligodendroglial tumors show loss of heterozygosity (LOH) for chromosome arms 1p and 19q. […] Further studies have shown that 1p/19q loss in fact results from a non-balanced translocation t (1:19) (q10:p10) with subsequent loss of one of the derivative chromosomes. […] This explains why it is the loss of the entire arms of 1p and 19q that is related to clinical outcome, rather than smaller terminal or interstitial deletions which occur by a completely different mechanism and are occasionally encountered in astrocytic tumors, such as glioblastoma. […] Recently, by using genome-wide, 50 base pair single-end sequencing, 1p/19q codeletion was demonstrated to be the only copy number aberration that was stable across spatial regions of low-grade diffuse gliomas and their recurrences. […] Virtually all 1p/19q codeleted tumors have a pro-neural expression profile, supporting the hypothesis that these gliomas originate from a bi-potential progenitor cell able to give rise to neurons and oligodendrocytes.

• #16 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazineccnuvincristine) chemotherapy, with virtually all tumors responding. […] In large prospective randomized studies on diffuse glioma, 1p/19q codeletion was associated with improved overall survival but also with increased benefit of adjuvant PCV chemotherapy given after radiotherapy. […] Following the initial discovery of isocitrate dehydrogenase (IDH) gene mutations in a small subset of especially younger glioblastoma patients with prolonged survival, a high percentage (70-80 %) of IDH1 and IDH2 mutations were identified in diffuse grade II and III gliomas, regardless of astrocytic or oligodendroglial cell type. […] Nearly all mutations involve codon 132 of IDH1 or the homologous codon 172 of IDH2, with c.395GA (p.R132H) representing 90 % of all IDH1 mutations. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100 %. […] Further studies have shown that IDH mutation is an early event in gliomagenesis (driver mutation), and likely precedes the development of the 1p/19q codeletion, the latter possibly specifically driving a diffuse glioma towards the classic oligodendroglioma morphologic phenotype, whereas superimposed TP53 and ATRX mutations drive it towards the astrocytoma phenotype instead.

• #17 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazineccnuvincristine) chemotherapy, with virtually all tumors responding. […] In large prospective randomized studies on diffuse glioma, 1p/19q codeletion was associated with improved overall survival but also with increased benefit of adjuvant PCV chemotherapy given after radiotherapy. […] Following the initial discovery of isocitrate dehydrogenase (IDH) gene mutations in a small subset of especially younger glioblastoma patients with prolonged survival, a high percentage (70-80 %) of IDH1 and IDH2 mutations were identified in diffuse grade II and III gliomas, regardless of astrocytic or oligodendroglial cell type. […] Nearly all mutations involve codon 132 of IDH1 or the homologous codon 172 of IDH2, with c.395GA (p.R132H) representing 90 % of all IDH1 mutations. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100 %. […] Further studies have shown that IDH mutation is an early event in gliomagenesis (driver mutation), and likely precedes the development of the 1p/19q codeletion, the latter possibly specifically driving a diffuse glioma towards the classic oligodendroglioma morphologic phenotype, whereas superimposed TP53 and ATRX mutations drive it towards the astrocytoma phenotype instead.

• #18 Diagnosis and Discussion – Case 1117 | Department of Pathology

  https://www.path.pitt.edu/diagnosis-and-discussion-case-1117

  Oligodendrogliomas most commonly present in the frontal lobe, with a median age of 43 at diagnosis, and classically present with seizures. […] Greater than 90% of IDH mutations in gliomas are of the canonical IDH1 p.R132H missense mutation, which is commonly screened for using immunohistochemistry with an antibody designed to recognize the IDH1 R132H mutant protein. […] Oligodendrogliomas without the IDH1 p.R132H mutation are more likely than similar astrocytomas to harbor an IDH2 mutation, which typically involves the codon for R172. […] While IDH-mutant glial neoplasms share the commonality of IDH alterations, they can typically be differentiated by additional genetic alterations that tend to segregate with oligodendroglial and astrocytic differentiation. 1p/19q codeletions are seen in oligodendrogliomas, as was identified in this case, and TERT promoter mutations are common.

• #19 Frontiers | Oligodendroglioma: A Review of Management and Pathways

  https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.722396/full

  IDH mutations identified in gliomas tend to occur at the active site of the enzyme at arginine 132 and 172 in IDH1 and IDH2, respectively. […] It was shown by Uhm (2010) that IDH mutations lead to the acquisition of a new enzymatic function that catalyzes the formation of D-2HG from alpha-KG. […] High mutant allele fractions have been found in patient samples at diagnosis and recurrence in tumor evolution studies. […] IDH mutated enzymes can promote proliferation and colony formation through its end metabolite 2-HG. […] The unbalanced translocation of the centromeric regions of chromosomes 1p and 19q attribute to the loss of the whole arm on both chromosomes. […] Following the stratification of AO according to 1p/19q co-deletion status, an in-depth genetic analysis of 1p/19q co-deleted tumors revealed inactivating mutations affecting the FUBP1 gene on chromosome 1p and the CIC gene on chromosome 19.

• #20 Oligodendroglioma | Concise Medical Knowledge

  https://www.lecturio.com/concepts/oligodendroglioma/

  Oligodendrogliomas are histologically defined tumors that include both isocitrate dehydrogenase (IDH) 1 and 2 mutations and codeletions of chromosomal arms 1p and 19q. […] Mutations in IDH1 (found in the cytosol) and/or IDH2 (found in the mitochondria): […] Mutations lead to production and buildup of 2-hydroxyglutarate (2-HG): […] 2-HG inhibits enzymatic function of -KG-dependent dioxygenases, which are involved in DNA demethylation. […] 2-HG causes epigenetic dysregulation can lead to tumor development. […] Codeletions of chromosomal arms 1p and 19q: […] Leads to epigenetic changes and hypermethylation of the genome. […] Other mutations: […] Activating mutations in the telomerase (TERT) promoter: […] Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter: MGMT is an enzyme involved in DNA repair.

• #21

  https://link.springer.com/article/10.1007/s00401-015-1424-1

  Through an altered substrate specificity, IDH mutations give rise to metabolic alterations, including an increase in production of 2-hydroxyglutarate (2-HG) which can inhibit histone demethylation and induces a glioma hypermethylation phenotype (glioma CpG island methylated phenotype or G-CIMP). […] In turn, this leads to a variety of downstream chromatin remodeling and transcriptional alterations. […] The presence of an IDH mutation may provide an opportunity to apply specific, IDH targeted treatment, no matter if the diagnosis was astrocytoma or (1p/19q codeleted) oligodendroglioma. […] This integrated diagnostic approach allows for much more robust recognition of biologically different subgroups within the spectrum of diffuse gliomas, thereby facilitating tailored treatment for individual patients.

• #22 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic changes, including altered DNA methylation and histone acetylation, with dysregulated signaling pathways like platelet-derived growth factor receptor (PDGFR) and the epidermal growth factor receptor (EGFR), further promote tumorigenesis. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] A hallmark of OGs is chromosomal arms 1p and 19q codeletion, which occurs in 70% to 90% of cases. […] Nearly all OGs harbor mutations in the IDH1 or IDH2 genes, producing the oncometabolite 2-hydroxyglutarate.

• #23 Oligodendroglioma | MedLink Neurology

  https://www.medlink.com/articles/oligodendroglioma

  Oligodendrogliomas are diffusely infiltrating chemoresponsive gliomas defined by the presence of mutated isocitrate dehydrogenase 1 (IDH1) or IDH2 and whole-arm chromosomal losses of 1p and 19q. […] The discovery of molecular and genetic alterations, such as simultaneous whole-arm deletions of chromosomes 1p and 19q (1p/19q codeletion) and mutations in isocitrate dehydrogenase (IDH), offered further insight into the biology and behavior of diffuse gliomas. […] IDH mutation leads to an accumulation of 2-hydroxyglutarate (2-HG), which has the downstream effects of inhibiting histone demethylation, subsequently impeding cell differentiation and leading to glioma formation. […] A subsequent event resulting in the unbalanced translocation of chromosomes 1p and 19q prompts the development of oligodendroglioma, presumably due to loss or alterations in tumor suppressor genes located on these loci.

• #24 Oligodendroglioma – Wikipedia

  https://en.wikipedia.org/wiki/Oligodendroglioma

  1p/19q co-deletion has been correlated with both chemosensitivity and improved prognosis in oligodendrogliomas. […] The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.

• #25 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Like other neoplasms, diffuse gliomas develop as a result of genetic and molecular alterations that further accumulate with tumor progression. […] These aberrations allow the tumor to acquire assets for sustained survival and growth and to escape normal growth restraining influences. […] Some of these molecular abnormalities carry important diagnostic, prognostic and/or predictive information, giving support for a major molecular component in future tumor characterization. […] The most promising markers for oligodendroglial tumors are briefly discussed below. […] In 1994, using restriction fragment length polymorphism analysis, Reifenberger et al. reported for the first time that many oligodendroglial tumors show loss of heterozygosity (LOH) for chromosome arms 1p and 19q. […] Further studies have shown that 1p/19q loss in fact results from a non-balanced translocation t (1:19) (q10:p10) with subsequent loss of one of the derivative chromosomes. […] This explains why it is the loss of the entire arms of 1p and 19q that is related to clinical outcome, rather than smaller terminal or interstitial deletions which occur by a completely different mechanism and are occasionally encountered in astrocytic tumors, such as glioblastoma. […] Recently, by using genome-wide, 50 base pair single-end sequencing, 1p/19q codeletion was demonstrated to be the only copy number aberration that was stable across spatial regions of low-grade diffuse gliomas and their recurrences. […] Virtually all 1p/19q codeleted tumors have a pro-neural expression profile, supporting the hypothesis that these gliomas originate from a bi-potential progenitor cell able to give rise to neurons and oligodendrocytes.

• #26 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Several other mutations have been identified in 1p/19q codeleted tumors. […] These include inactivating mutations in the homolog of the Drosophila capicua (CIC) and far-upstream binding protein 1 (FUBP1) gene, considered to occur secondary to the unbalanced translocation and found to be present in ~50-70 % and 15-30 % of 1p/19q codeleted tumors, respectively. […] These genes are located on the 19q (CIC) and 1p (FUBP1) chromosomal arms, supporting their putative roles as tumor suppressor genes. […] The higher rate of CIC mutations in pure oligodendrogliomas suggests CIC mutations may be related to the phenotypic characteristics of these tumors. […] Two mutually exclusive mutations play a role in telomere maintenance in gliomas: telomerase reverse transcriptase (TERT) mutations in hot spot promoter regions C228T, C250T result in increased expression of telomerase. […] Paradoxically, these mutations are present in both 1p/19q codeleted oligodendrogliomas and in IDH wild type high-grade gliomas. […] Virtually all 1p/19q codeleted tumors carry TERT mutations. […] Gliomas with TERT mutations in the presence of 1p/19q codeletion (i.e., oligodendrogliomas), have a very favorable outcome where the same TERT mutations in the absence of this codeletion or IDH mutations herald a grim prognosis (comparable to glioblastoma).

• #27 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Several other mutations have been identified in 1p/19q codeleted tumors. […] These include inactivating mutations in the homolog of the Drosophila capicua (CIC) and far-upstream binding protein 1 (FUBP1) gene, considered to occur secondary to the unbalanced translocation and found to be present in ~50-70 % and 15-30 % of 1p/19q codeleted tumors, respectively. […] These genes are located on the 19q (CIC) and 1p (FUBP1) chromosomal arms, supporting their putative roles as tumor suppressor genes. […] The higher rate of CIC mutations in pure oligodendrogliomas suggests CIC mutations may be related to the phenotypic characteristics of these tumors. […] Two mutually exclusive mutations play a role in telomere maintenance in gliomas: telomerase reverse transcriptase (TERT) mutations in hot spot promoter regions C228T, C250T result in increased expression of telomerase. […] Paradoxically, these mutations are present in both 1p/19q codeleted oligodendrogliomas and in IDH wild type high-grade gliomas. […] Virtually all 1p/19q codeleted tumors carry TERT mutations. […] Gliomas with TERT mutations in the presence of 1p/19q codeletion (i.e., oligodendrogliomas), have a very favorable outcome where the same TERT mutations in the absence of this codeletion or IDH mutations herald a grim prognosis (comparable to glioblastoma).

• #28 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Several other mutations have been identified in 1p/19q codeleted tumors. […] These include inactivating mutations in the homolog of the Drosophila capicua (CIC) and far-upstream binding protein 1 (FUBP1) gene, considered to occur secondary to the unbalanced translocation and found to be present in ~50-70 % and 15-30 % of 1p/19q codeleted tumors, respectively. […] These genes are located on the 19q (CIC) and 1p (FUBP1) chromosomal arms, supporting their putative roles as tumor suppressor genes. […] The higher rate of CIC mutations in pure oligodendrogliomas suggests CIC mutations may be related to the phenotypic characteristics of these tumors. […] Two mutually exclusive mutations play a role in telomere maintenance in gliomas: telomerase reverse transcriptase (TERT) mutations in hot spot promoter regions C228T, C250T result in increased expression of telomerase. […] Paradoxically, these mutations are present in both 1p/19q codeleted oligodendrogliomas and in IDH wild type high-grade gliomas. […] Virtually all 1p/19q codeleted tumors carry TERT mutations. […] Gliomas with TERT mutations in the presence of 1p/19q codeletion (i.e., oligodendrogliomas), have a very favorable outcome where the same TERT mutations in the absence of this codeletion or IDH mutations herald a grim prognosis (comparable to glioblastoma).

• #29 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Several other mutations have been identified in 1p/19q codeleted tumors. […] These include inactivating mutations in the homolog of the Drosophila capicua (CIC) and far-upstream binding protein 1 (FUBP1) gene, considered to occur secondary to the unbalanced translocation and found to be present in ~50-70 % and 15-30 % of 1p/19q codeleted tumors, respectively. […] These genes are located on the 19q (CIC) and 1p (FUBP1) chromosomal arms, supporting their putative roles as tumor suppressor genes. […] The higher rate of CIC mutations in pure oligodendrogliomas suggests CIC mutations may be related to the phenotypic characteristics of these tumors. […] Two mutually exclusive mutations play a role in telomere maintenance in gliomas: telomerase reverse transcriptase (TERT) mutations in hot spot promoter regions C228T, C250T result in increased expression of telomerase. […] Paradoxically, these mutations are present in both 1p/19q codeleted oligodendrogliomas and in IDH wild type high-grade gliomas. […] Virtually all 1p/19q codeleted tumors carry TERT mutations. […] Gliomas with TERT mutations in the presence of 1p/19q codeletion (i.e., oligodendrogliomas), have a very favorable outcome where the same TERT mutations in the absence of this codeletion or IDH mutations herald a grim prognosis (comparable to glioblastoma).

• #30 Frontiers | Oligodendroglioma: A Review of Management and Pathways

  https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.722396/full

  These alterations have correlated with a shorter event free survival (EFS; 29 vs. 53 months, p < 0.0001) and OS (48 vs. 83 months, p < 0.0001). [...] TERT mutations in glioma are often found within the promoter region. [...] TERT reactivation then takes place when GA-binding protein (GABP) transcription factor binds to the mutant TERT promoter. [...] The CODEL study is a phase 3 study whereby 36 patients with newly diagnosed grade III oligodendrogliomas were randomized to receive RT alone (Arm A), RT with concomitant and adjuvant TMZ (Arm B) or TMZ alone (Arm C) (Jaeckle et al., 2021). [...] AO remains an understudied tumor with several unclear pathogenic pathways.

• #31 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  O6-alkylguanine-DNA-alkyltransferase (AGT), encoded by the O6-methylguanine-DNA-methyltransferase (MGMT) gene, is a key repair enzyme that removes alkyl and methyl adducts from DNA, making cells with functional enzyme less sensitive to alkylating and methylating chemotherapy than those incapable of repairing these adducts. […] Indeed, gliomas with MGMT promoter methylation were demonstrated to be more sensitive to the alkylating agent temozolomide. […] Several studies have shown a high rate of MGMT promoter methylation in grade II and III gliomas, which subsequently was demonstrated to be related to IDH mutational status and G-CIMP. […] These findings at least partly explain the favorable outcome of MGMT methylated tumors after not only chemotherapy or combined chemoradiotherapy, but also after radiotherapy only.

• #32 Oligodendroglioma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Oligodendroglioma_pathophysiology

  Oligodendroglioma arises from the tripotential glial precursor cells and not from the bipotential oligodendrocytes. […] Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53, MGMT, TP73, BRAF, EGFR, and PTEN. […] Development of oligodendroglioma is the result of multiple genetic mutations. […] There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.

• #33 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic changes, including altered DNA methylation and histone acetylation, with dysregulated signaling pathways like platelet-derived growth factor receptor (PDGFR) and the epidermal growth factor receptor (EGFR), further promote tumorigenesis. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] A hallmark of OGs is chromosomal arms 1p and 19q codeletion, which occurs in 70% to 90% of cases. […] Nearly all OGs harbor mutations in the IDH1 or IDH2 genes, producing the oncometabolite 2-hydroxyglutarate.

• #34 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic changes, including altered DNA methylation and histone acetylation, with dysregulated signaling pathways like platelet-derived growth factor receptor (PDGFR) and the epidermal growth factor receptor (EGFR), further promote tumorigenesis. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] A hallmark of OGs is chromosomal arms 1p and 19q codeletion, which occurs in 70% to 90% of cases. […] Nearly all OGs harbor mutations in the IDH1 or IDH2 genes, producing the oncometabolite 2-hydroxyglutarate.

• #35 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic changes, including altered DNA methylation and histone acetylation, with dysregulated signaling pathways like platelet-derived growth factor receptor (PDGFR) and the epidermal growth factor receptor (EGFR), further promote tumorigenesis. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] A hallmark of OGs is chromosomal arms 1p and 19q codeletion, which occurs in 70% to 90% of cases. […] Nearly all OGs harbor mutations in the IDH1 or IDH2 genes, producing the oncometabolite 2-hydroxyglutarate.

• #36 Multi-faceted computational assessment of risk and progression in oligodendroglioma implicates NOTCH and PI3K pathways | npj Precision Oncology

  https://www.nature.com/articles/s41698-018-0067-9

  Oligodendrogliomas are diffusely infiltrative gliomas defined by IDH-mutation and co-deletion of 1p/19q. […] Our multi-faceted computational approach uncovered key genetic alterations associated with disease progression and shorter survival in oligodendroglioma and specifically identified Notch pathway inactivation and PI3K pathway activation as the most strongly associated with MRI and pathology findings of advanced disease and poor clinical outcome. […] Our approach confirmed the association of NOTCH1 mutations with disease progression and shorter survival in oligodendroglioma, and further uncovered aberrant regulation of Notch and PI3K pathways as most strongly associated with advanced disease. […] Our results suggest inactivation of Notch signaling may be more relevant to oligodendroglioma progression than NOTCH1 mutations alone.

• #37 Multi-faceted computational assessment of risk and progression in oligodendroglioma implicates NOTCH and PI3K pathways | npj Precision Oncology

  https://www.nature.com/articles/s41698-018-0067-9

  Oligodendrogliomas are diffusely infiltrative gliomas defined by IDH-mutation and co-deletion of 1p/19q. […] Our multi-faceted computational approach uncovered key genetic alterations associated with disease progression and shorter survival in oligodendroglioma and specifically identified Notch pathway inactivation and PI3K pathway activation as the most strongly associated with MRI and pathology findings of advanced disease and poor clinical outcome. […] Our approach confirmed the association of NOTCH1 mutations with disease progression and shorter survival in oligodendroglioma, and further uncovered aberrant regulation of Notch and PI3K pathways as most strongly associated with advanced disease. […] Our results suggest inactivation of Notch signaling may be more relevant to oligodendroglioma progression than NOTCH1 mutations alone.

• #38 Multi-faceted computational assessment of risk and progression in oligodendroglioma implicates NOTCH and PI3K pathways | npj Precision Oncology

  https://www.nature.com/articles/s41698-018-0067-9

  Furthermore, we found mutations and deletions of RBPJ, the nuclear binding partner of NOTCH1 and a member of the canonical Notch pathway, are linked to advanced disease, providing additional evidence that Notch pathway inactivation may be a general progression mechanism. […] Our identification of Notch and PI3K pathways association with survival risk and disease progression does not demonstrate a causal or temporal relationship, and represents an inherent limitation of our study.

• #39 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  EGFR amplifications are virtually mutually exclusive with 1p/19q codeletion and with IDH mutations. […] This suggests that these tumors follow a different oncogenic route from the start. […] The presence of polysomy of chromosome 7 and amplification of the epidermal growth factor receptor (EGFR) gene is associated with TERT mutations and a prognosis similar to primary glioblastoma in general. […] Anaplastic oligodendroglial tumors usually have additional genetic aberrations, in particular 9p LOH and/or deletion of the CDKN2A gene (p16), PIK3CA mutations, and polysomies. […] Recent data of The Cancer Genome Atlas (TCGA) consortium on lower grade (WHO grade II and III) gliomas show that IDH mutations in these gliomas are virtually mutually exclusive with homozygous deletion of CDKN2A and with amplification of EGFR.

• #40 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  EGFR amplifications are virtually mutually exclusive with 1p/19q codeletion and with IDH mutations. […] This suggests that these tumors follow a different oncogenic route from the start. […] The presence of polysomy of chromosome 7 and amplification of the epidermal growth factor receptor (EGFR) gene is associated with TERT mutations and a prognosis similar to primary glioblastoma in general. […] Anaplastic oligodendroglial tumors usually have additional genetic aberrations, in particular 9p LOH and/or deletion of the CDKN2A gene (p16), PIK3CA mutations, and polysomies. […] Recent data of The Cancer Genome Atlas (TCGA) consortium on lower grade (WHO grade II and III) gliomas show that IDH mutations in these gliomas are virtually mutually exclusive with homozygous deletion of CDKN2A and with amplification of EGFR.

• #41 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  EGFR amplifications are virtually mutually exclusive with 1p/19q codeletion and with IDH mutations. […] This suggests that these tumors follow a different oncogenic route from the start. […] The presence of polysomy of chromosome 7 and amplification of the epidermal growth factor receptor (EGFR) gene is associated with TERT mutations and a prognosis similar to primary glioblastoma in general. […] Anaplastic oligodendroglial tumors usually have additional genetic aberrations, in particular 9p LOH and/or deletion of the CDKN2A gene (p16), PIK3CA mutations, and polysomies. […] Recent data of The Cancer Genome Atlas (TCGA) consortium on lower grade (WHO grade II and III) gliomas show that IDH mutations in these gliomas are virtually mutually exclusive with homozygous deletion of CDKN2A and with amplification of EGFR.

• #42 Extracranial metastatic oligodendroglioma with molecular progression, case presentation | Diagnostic Pathology | Full Text

  https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-024-01529-7

  Notably, the combination of gain of chromosome 7 and loss of chromosome 10 (+7/-10) is a characteristic molecular signature for IDH-wild-type glioblastoma and may indicate molecular progression of the oligodendroglioma. […] We identified molecular progression in the metastasis that, to the best of our knowledge, has not been previously described in metastatic oligodendroglioma.

• #43 Oligodendroglioma | MedLink Neurology

  https://www.medlink.com/articles/oligodendroglioma

  The driver mutations associated with transformation to grade 3 have not been fully elucidated either, though deletion of chromosome 9p (resulting in loss of the CDKN2A locus) correlated with genomic instability, high vascular endothelial growth factor (VEGF) expression, and poor survival appears to play a role. […] The incorporation of specific molecular and genetic features to the diagnostic criteria improves interobserver variability; thus, a fully-characterized oligodendroglioma is defined by a histopathologic appearance of oligodendroglioma along with IDH-mutation and combined whole-arm loss of chromosomes 1p and 19q.

• #44 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic changes, including altered DNA methylation and histone acetylation, with dysregulated signaling pathways like platelet-derived growth factor receptor (PDGFR) and the epidermal growth factor receptor (EGFR), further promote tumorigenesis. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] A hallmark of OGs is chromosomal arms 1p and 19q codeletion, which occurs in 70% to 90% of cases. […] Nearly all OGs harbor mutations in the IDH1 or IDH2 genes, producing the oncometabolite 2-hydroxyglutarate.

• #45 Oligodendroglioma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559184/

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic modifications, including DNA hypermethylation and histone changes, further contribute to tumor development by altering gene expression and cell differentiation. […] Dysregulated signaling pathways, such as those involving PDGFR, EGFR, and phosphoinositide 3-kinase (PI3K), drive tumor cell proliferation, angiogenesis, and resistance to apoptosis. […] The tumor microenvironment, characterized by hypoxia, inflammation, and immune evasion, plays an additional role in sustaining tumor progression. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] Advanced understanding of the tumor microenvironment and genetic drivers continues to shape the management of OGs.

• #46 Pathology & Oncology Research | Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma

  https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609844/full

  Vasculogenic mimicry (VM) has been identified as an important vasculogenic mechanism in malignant tumors, but little is known about its clinical meanings and mechanisms in oligodendroglioma. […] VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (rs = 0.435, p < 0.001 and rs = 0.317, p < 0.001). [...] Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients (p < 0.001, HR = 7.928, 95%CI: 3.382–18.584, and p = 0.007, HR = 4.534, 95%CI: 1.504–13.675, respectively). [...] The role of VM in tumor progression and the implication of pATM/pATR in VM formation may provide potential therapeutic targets for oligodendroglioma treatment. [...] The activation of ATM and/or ATR in cancer cells contributes to treatment resistance and is evaluated as prognostic indexes.

• #47 Pathology & Oncology Research | Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma

  https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609844/full

  Higher pATM was significantly correlated with higher WHO grade (p < 0.001) and recurrent tumor (p = 0.01). [...] The results remind us the correlation between VM formation and tumor grade and recurrence, suggesting a probable link between VM formation and ATM/ATR activation. [...] Activation of ATM/ATR but not HIF1α correlates with VM formation in oligodendrogliomas. [...] In summary, activation of ATM/ATR but not HIF1α shows a positive correlation with VM formation in oligodendroglioma patients. [...] The levels of pATM/pATR in oligodendrogliomas may be associated with the progression but not overall growth of tumors, which recapitulates the situation of VM formation. [...] VM presents as a potential unfavorable predictor for progression in oligodendroglioma patients. Activated ATM and ATR are supposed to participate in VM formation which is implied by the positive correlation between them.

• #48 Pathology & Oncology Research | Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma

  https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609844/full

  Higher pATM was significantly correlated with higher WHO grade (p < 0.001) and recurrent tumor (p = 0.01). [...] The results remind us the correlation between VM formation and tumor grade and recurrence, suggesting a probable link between VM formation and ATM/ATR activation. [...] Activation of ATM/ATR but not HIF1α correlates with VM formation in oligodendrogliomas. [...] In summary, activation of ATM/ATR but not HIF1α shows a positive correlation with VM formation in oligodendroglioma patients. [...] The levels of pATM/pATR in oligodendrogliomas may be associated with the progression but not overall growth of tumors, which recapitulates the situation of VM formation. [...] VM presents as a potential unfavorable predictor for progression in oligodendroglioma patients. Activated ATM and ATR are supposed to participate in VM formation which is implied by the positive correlation between them.

• #49 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazineccnuvincristine) chemotherapy, with virtually all tumors responding. […] In large prospective randomized studies on diffuse glioma, 1p/19q codeletion was associated with improved overall survival but also with increased benefit of adjuvant PCV chemotherapy given after radiotherapy. […] Following the initial discovery of isocitrate dehydrogenase (IDH) gene mutations in a small subset of especially younger glioblastoma patients with prolonged survival, a high percentage (70-80 %) of IDH1 and IDH2 mutations were identified in diffuse grade II and III gliomas, regardless of astrocytic or oligodendroglial cell type. […] Nearly all mutations involve codon 132 of IDH1 or the homologous codon 172 of IDH2, with c.395GA (p.R132H) representing 90 % of all IDH1 mutations. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100 %. […] Further studies have shown that IDH mutation is an early event in gliomagenesis (driver mutation), and likely precedes the development of the 1p/19q codeletion, the latter possibly specifically driving a diffuse glioma towards the classic oligodendroglioma morphologic phenotype, whereas superimposed TP53 and ATRX mutations drive it towards the astrocytoma phenotype instead.

• #50 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazineccnuvincristine) chemotherapy, with virtually all tumors responding. […] In large prospective randomized studies on diffuse glioma, 1p/19q codeletion was associated with improved overall survival but also with increased benefit of adjuvant PCV chemotherapy given after radiotherapy. […] Following the initial discovery of isocitrate dehydrogenase (IDH) gene mutations in a small subset of especially younger glioblastoma patients with prolonged survival, a high percentage (70-80 %) of IDH1 and IDH2 mutations were identified in diffuse grade II and III gliomas, regardless of astrocytic or oligodendroglial cell type. […] Nearly all mutations involve codon 132 of IDH1 or the homologous codon 172 of IDH2, with c.395GA (p.R132H) representing 90 % of all IDH1 mutations. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100 %. […] Further studies have shown that IDH mutation is an early event in gliomagenesis (driver mutation), and likely precedes the development of the 1p/19q codeletion, the latter possibly specifically driving a diffuse glioma towards the classic oligodendroglioma morphologic phenotype, whereas superimposed TP53 and ATRX mutations drive it towards the astrocytoma phenotype instead.

• #51 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Several other mutations have been identified in 1p/19q codeleted tumors. […] These include inactivating mutations in the homolog of the Drosophila capicua (CIC) and far-upstream binding protein 1 (FUBP1) gene, considered to occur secondary to the unbalanced translocation and found to be present in ~50-70 % and 15-30 % of 1p/19q codeleted tumors, respectively. […] These genes are located on the 19q (CIC) and 1p (FUBP1) chromosomal arms, supporting their putative roles as tumor suppressor genes. […] The higher rate of CIC mutations in pure oligodendrogliomas suggests CIC mutations may be related to the phenotypic characteristics of these tumors. […] Two mutually exclusive mutations play a role in telomere maintenance in gliomas: telomerase reverse transcriptase (TERT) mutations in hot spot promoter regions C228T, C250T result in increased expression of telomerase. […] Paradoxically, these mutations are present in both 1p/19q codeleted oligodendrogliomas and in IDH wild type high-grade gliomas. […] Virtually all 1p/19q codeleted tumors carry TERT mutations. […] Gliomas with TERT mutations in the presence of 1p/19q codeletion (i.e., oligodendrogliomas), have a very favorable outcome where the same TERT mutations in the absence of this codeletion or IDH mutations herald a grim prognosis (comparable to glioblastoma).

• #52 1p/19q Co-deletion in Glioma: ESMO Biomarker Factsheet

  https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/1p-19q-co-deletion-in-glioma

  Other common molecular alterations co-occurring with 1p/19q co-deletion include mutations in the telomerase reverse transcriptase (TERT) gene promoter, mutations in homolog of Drosophila capicua (CIC) and far upstream element binding protein (FUBP1), and promoter methylation of the methyl-guanine methyl transferase (MGMT) gene. […] With very few exceptions, 1p/19q co-deletion is mutually exclusive with TP53 and ATRX mutation, which both characterize glial tumours of astrocytic lineage. […] Thereby, assessment of 1p/19q co-deletion, together with IDH mutation status and other molecular markers (e.g. ATRX and TP53 status), can help distinguish oligodendrogliomas which are IDH-mutant and 1p/19q-codeleted, from tumours of astrocytic lineage which are 1p/19q-non co-deleted. […] The presence of 1p/19q co-deletion is a strong independent prognostic biomarker associated with improved survival in both diffuse low-grade and anaplastic tumours.

• #53 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  EGFR amplifications are virtually mutually exclusive with 1p/19q codeletion and with IDH mutations. […] This suggests that these tumors follow a different oncogenic route from the start. […] The presence of polysomy of chromosome 7 and amplification of the epidermal growth factor receptor (EGFR) gene is associated with TERT mutations and a prognosis similar to primary glioblastoma in general. […] Anaplastic oligodendroglial tumors usually have additional genetic aberrations, in particular 9p LOH and/or deletion of the CDKN2A gene (p16), PIK3CA mutations, and polysomies. […] Recent data of The Cancer Genome Atlas (TCGA) consortium on lower grade (WHO grade II and III) gliomas show that IDH mutations in these gliomas are virtually mutually exclusive with homozygous deletion of CDKN2A and with amplification of EGFR.

• #54 Oligodendroglioma | MedLink Neurology

  https://www.medlink.com/articles/oligodendroglioma

  The driver mutations associated with transformation to grade 3 have not been fully elucidated either, though deletion of chromosome 9p (resulting in loss of the CDKN2A locus) correlated with genomic instability, high vascular endothelial growth factor (VEGF) expression, and poor survival appears to play a role. […] The incorporation of specific molecular and genetic features to the diagnostic criteria improves interobserver variability; thus, a fully-characterized oligodendroglioma is defined by a histopathologic appearance of oligodendroglioma along with IDH-mutation and combined whole-arm loss of chromosomes 1p and 19q.

• #55 Oligodendroglioma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559184/

  Mutations in IDH1 and IDH2 further characterize these tumors, contributing to the glioma CpG island methylator phenotype (G-CIMP), which alters deoxyribonucleic acid (DNA) methylation and promotes growth. […] Epigenetic modifications, including DNA hypermethylation and histone changes, further contribute to tumor development by altering gene expression and cell differentiation. […] Dysregulated signaling pathways, such as those involving PDGFR, EGFR, and phosphoinositide 3-kinase (PI3K), drive tumor cell proliferation, angiogenesis, and resistance to apoptosis. […] The tumor microenvironment, characterized by hypoxia, inflammation, and immune evasion, plays an additional role in sustaining tumor progression. […] Combining these factors transforms normal oligodendrocytes or their precursors into malignant cells, giving rise to OGs. […] Advanced understanding of the tumor microenvironment and genetic drivers continues to shape the management of OGs.

• #56 Oligodendroglioma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26152

  This molecule induces a G-CIMP methylator phenotype, promoting DNA hypermethylation, impairing cellular differentiation, and facilitating tumor growth. […] Epigenetic modifications, including DNA hypermethylation and histone changes, further contribute to tumor development by altering gene expression and cell differentiation. […] Dysregulated signaling pathways, such as those involving PDGFR, EGFR, and phosphoinositide 3-kinase (PI3K), drive tumor cell proliferation, angiogenesis, and resistance to apoptosis. […] The tumor microenvironment, characterized by hypoxia, inflammation, and immune evasion, plays an additional role in sustaining tumor progression. […] Historically, OGs were thought to originate from mature oligodendrocytes. However, recent evidence suggests that they arise from neuroprogenitor cells with glial precursor characteristics.

• #57

  https://link.springer.com/article/10.1007/s00401-015-1424-1

  Through an altered substrate specificity, IDH mutations give rise to metabolic alterations, including an increase in production of 2-hydroxyglutarate (2-HG) which can inhibit histone demethylation and induces a glioma hypermethylation phenotype (glioma CpG island methylated phenotype or G-CIMP). […] In turn, this leads to a variety of downstream chromatin remodeling and transcriptional alterations. […] The presence of an IDH mutation may provide an opportunity to apply specific, IDH targeted treatment, no matter if the diagnosis was astrocytoma or (1p/19q codeleted) oligodendroglioma. […] This integrated diagnostic approach allows for much more robust recognition of biologically different subgroups within the spectrum of diffuse gliomas, thereby facilitating tailored treatment for individual patients.

• #58 Clinical features, diagnosis, and pathology of IDH-mutant, 1p/19q-codeleted oligodendrogliomas – UpToDate

  https://www.uptodate.com/contents/clinical-features-diagnosis-and-pathology-of-idh-mutant-1p-19q-codeleted-oligodendrogliomas

  There are significant differences between oligodendrogliomas and other glial tumors in pathology, molecular pathogenesis, and natural history. These differences have important prognostic implications, which can affect treatment. […] In the World Health Organization (WHO) classification of central nervous system tumors, oligodendroglial tumors are defined by molecular diagnostics to include only those diffuse gliomas harboring both a mutation in isocitrate dehydrogenase (IDH) type 1 or type 2 and codeletion of chromosomes 1p and 19q. […] The clinical manifestations, classification, pathologic classification, and molecular prognostic factors associated with IDH-mutant, 1p/19q-codeleted oligodendrogliomas (grades 2 and 3) will be reviewed here.

• #59

  https://journals.lww.com/neur/fulltext/2022/70030/clinical_profile,_pathology,_and_molecular_typing.29.aspx

  Diffuse gliomas are represented in the 2007 WHO classification of CNS tumors as astrocytomas, oligoastrocytoma, and oligodendroglioma of grades II/III and glioblastomas WHO grade IV, which was a pure morphologic classification. […] The WHO 2016 classification combines morphology with molecular markers like IDH, ATRX, and 1p/19q codeletion to give an integrated diagnosis. […] The study emphasizes the need for molecular work up of tumors with oligodendroglial morphology with readily available techniques like IHC and Fluorescence in situ hybridization. […] Molecular profile is mandatory for subtyping of diffuse gliomas with oligodendroglial morphology. […] The WHO 2016 classification of CNS tumors classifies oligodendrogliomas with essential molecular work up into grade II and grade III tumors and those with incomplete molecular work up into oligodendroglioma grade II/III NOS.

• #60 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. […] Roughly 20 years ago, the first glioma-associated molecular signature was found with complete chromosome 1p and 19q codeletion being particularly common in histologically classic oligodendrogliomas. […] Subsequently, this codeletion appeared to not only carry diagnostic, but also prognostic and predictive information, the latter aspect only recently resolved after carefully constructed clinical trials with very long follow-up times. […] More recently described biomarkers, including the non-balanced translocation leading to 1p/19q codeletion, promoter hypermethylation of the MGMT gene, mutations of the IDH1 or IDH2 gene, and mutations of FUBP1 (on 1p) or CIC (on 19q), have greatly enhanced our understanding of oligodendroglioma biology, although their diagnostic, prognostic, and predictive roles are less clear. […] It has therefore been suggested that complete 1p/19q codeletion be required for the diagnosis of canonical oligodendroglioma. […] This transition to an integrated morphological and molecular diagnosis may result in the disappearance of oligoastrocytoma as an entity, but brings new challenges as well. […] For instance it needs to be sorted out how (histopathological) criteria for grading of canonical oligodendrogliomas should be adapted, how pediatric oligodendrogliomas (known to lack codeletions) should be defined, which platforms and cut-off levels should ideally be used for demonstration of particular molecular aberrations, and how the diagnosis of oligodendroglioma should be made in centers/countries where molecular diagnostics is not available. […] Meanwhile, smart integration of morphological and molecular information will lead to recognition of biologically much more uniform groups within the spectrum of diffuse gliomas and thereby facilitate tailored treatments for individual patients.

• #61 1p/19q Co-deletion in Glioma: ESMO Biomarker Factsheet

  https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/1p-19q-co-deletion-in-glioma

  Other common molecular alterations co-occurring with 1p/19q co-deletion include mutations in the telomerase reverse transcriptase (TERT) gene promoter, mutations in homolog of Drosophila capicua (CIC) and far upstream element binding protein (FUBP1), and promoter methylation of the methyl-guanine methyl transferase (MGMT) gene. […] With very few exceptions, 1p/19q co-deletion is mutually exclusive with TP53 and ATRX mutation, which both characterize glial tumours of astrocytic lineage. […] Thereby, assessment of 1p/19q co-deletion, together with IDH mutation status and other molecular markers (e.g. ATRX and TP53 status), can help distinguish oligodendrogliomas which are IDH-mutant and 1p/19q-codeleted, from tumours of astrocytic lineage which are 1p/19q-non co-deleted. […] The presence of 1p/19q co-deletion is a strong independent prognostic biomarker associated with improved survival in both diffuse low-grade and anaplastic tumours.

• #62 1p/19q Co-deletion in Glioma: ESMO Biomarker Factsheet

  https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/1p-19q-co-deletion-in-glioma

  Among all diffuse gliomas, patients with 1p/19q-co-deletion have the most favourable prognosis. […] 1p/19q-co-deletion has predictive value for response to chemotherapy in anaplastic oligodendrogliomas. […] Extended follow-up of two large randomised controlled trials that compared procarbazine/lomustine/vincristine (PCV) chemotherapy in combination with radiotherapy to radiotherapy alone demonstrated a survival advantage of first-line chemotherapy in 1p/19q-co-deleted oligodendrogliomas. […] FISH is unable to differentiate between the whole chromosome arm deletions with centromeric breakpoints characteristic of 1p/19q co-deleted oligodendrogliomas, from smaller focal deletions. […] This distinction is important given the association of 1p/19q whole-arm co-deletion with improved survival and response to chemotherapy in the oligodendroglial tumour subtype.

• #63 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  Several other mutations have been identified in 1p/19q codeleted tumors. […] These include inactivating mutations in the homolog of the Drosophila capicua (CIC) and far-upstream binding protein 1 (FUBP1) gene, considered to occur secondary to the unbalanced translocation and found to be present in ~50-70 % and 15-30 % of 1p/19q codeleted tumors, respectively. […] These genes are located on the 19q (CIC) and 1p (FUBP1) chromosomal arms, supporting their putative roles as tumor suppressor genes. […] The higher rate of CIC mutations in pure oligodendrogliomas suggests CIC mutations may be related to the phenotypic characteristics of these tumors. […] Two mutually exclusive mutations play a role in telomere maintenance in gliomas: telomerase reverse transcriptase (TERT) mutations in hot spot promoter regions C228T, C250T result in increased expression of telomerase. […] Paradoxically, these mutations are present in both 1p/19q codeleted oligodendrogliomas and in IDH wild type high-grade gliomas. […] Virtually all 1p/19q codeleted tumors carry TERT mutations. […] Gliomas with TERT mutations in the presence of 1p/19q codeletion (i.e., oligodendrogliomas), have a very favorable outcome where the same TERT mutations in the absence of this codeletion or IDH mutations herald a grim prognosis (comparable to glioblastoma).

• #64 1p/19q Co-deletion in Glioma: ESMO Biomarker Factsheet

  https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/1p-19q-co-deletion-in-glioma

  Among all diffuse gliomas, patients with 1p/19q-co-deletion have the most favourable prognosis. […] 1p/19q-co-deletion has predictive value for response to chemotherapy in anaplastic oligodendrogliomas. […] Extended follow-up of two large randomised controlled trials that compared procarbazine/lomustine/vincristine (PCV) chemotherapy in combination with radiotherapy to radiotherapy alone demonstrated a survival advantage of first-line chemotherapy in 1p/19q-co-deleted oligodendrogliomas. […] FISH is unable to differentiate between the whole chromosome arm deletions with centromeric breakpoints characteristic of 1p/19q co-deleted oligodendrogliomas, from smaller focal deletions. […] This distinction is important given the association of 1p/19q whole-arm co-deletion with improved survival and response to chemotherapy in the oligodendroglial tumour subtype.

• #65 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazineccnuvincristine) chemotherapy, with virtually all tumors responding. […] In large prospective randomized studies on diffuse glioma, 1p/19q codeletion was associated with improved overall survival but also with increased benefit of adjuvant PCV chemotherapy given after radiotherapy. […] Following the initial discovery of isocitrate dehydrogenase (IDH) gene mutations in a small subset of especially younger glioblastoma patients with prolonged survival, a high percentage (70-80 %) of IDH1 and IDH2 mutations were identified in diffuse grade II and III gliomas, regardless of astrocytic or oligodendroglial cell type. […] Nearly all mutations involve codon 132 of IDH1 or the homologous codon 172 of IDH2, with c.395GA (p.R132H) representing 90 % of all IDH1 mutations. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100 %. […] Further studies have shown that IDH mutation is an early event in gliomagenesis (driver mutation), and likely precedes the development of the 1p/19q codeletion, the latter possibly specifically driving a diffuse glioma towards the classic oligodendroglioma morphologic phenotype, whereas superimposed TP53 and ATRX mutations drive it towards the astrocytoma phenotype instead.

• #66

  https://link.springer.com/article/10.1007/s00401-015-1424-1

  The most promising markers for oligodendroglial tumors are briefly discussed below. […] In 1994, using restriction fragment length polymorphism analysis, Reifenberger et al. reported for the first time that many oligodendroglial tumors show loss of heterozygosity (LOH) for chromosome arms 1p and 19q. […] The high clinical relevance of 1p/19q loss became clear when this marker appeared to be associated with sensitivity to chemotherapy and improved outcome. […] Cairncross et al. were the first to point out that recurrent anaplastic oligodendrogliomas with 1p/19q codeletion were far more responsive to PCV (procarbazine-ccnuvincristine) chemotherapy, with virtually all tumors responding. […] The IDH1 R132H mutant protein can be detected reliably using immunohistochemistry. […] The IDH mutation rate in 1p/19q codeleted tumors approaches 100%.

• #67 1p/19q Co-deletion in Glioma: ESMO Biomarker Factsheet

  https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/1p-19q-co-deletion-in-glioma

  Among all diffuse gliomas, patients with 1p/19q-co-deletion have the most favourable prognosis. […] 1p/19q-co-deletion has predictive value for response to chemotherapy in anaplastic oligodendrogliomas. […] Extended follow-up of two large randomised controlled trials that compared procarbazine/lomustine/vincristine (PCV) chemotherapy in combination with radiotherapy to radiotherapy alone demonstrated a survival advantage of first-line chemotherapy in 1p/19q-co-deleted oligodendrogliomas. […] FISH is unable to differentiate between the whole chromosome arm deletions with centromeric breakpoints characteristic of 1p/19q co-deleted oligodendrogliomas, from smaller focal deletions. […] This distinction is important given the association of 1p/19q whole-arm co-deletion with improved survival and response to chemotherapy in the oligodendroglial tumour subtype.

• #68 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  O6-alkylguanine-DNA-alkyltransferase (AGT), encoded by the O6-methylguanine-DNA-methyltransferase (MGMT) gene, is a key repair enzyme that removes alkyl and methyl adducts from DNA, making cells with functional enzyme less sensitive to alkylating and methylating chemotherapy than those incapable of repairing these adducts. […] Indeed, gliomas with MGMT promoter methylation were demonstrated to be more sensitive to the alkylating agent temozolomide. […] Several studies have shown a high rate of MGMT promoter methylation in grade II and III gliomas, which subsequently was demonstrated to be related to IDH mutational status and G-CIMP. […] These findings at least partly explain the favorable outcome of MGMT methylated tumors after not only chemotherapy or combined chemoradiotherapy, but also after radiotherapy only.

• #69 Oligodendroglioma: pathology, molecular mechanisms and markers

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4436696/

  For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. […] Roughly 20 years ago, the first glioma-associated molecular signature was found with complete chromosome 1p and 19q codeletion being particularly common in histologically classic oligodendrogliomas. […] Subsequently, this codeletion appeared to not only carry diagnostic, but also prognostic and predictive information, the latter aspect only recently resolved after carefully constructed clinical trials with very long follow-up times. […] More recently described biomarkers, including the non-balanced translocation leading to 1p/19q codeletion, promoter hypermethylation of the MGMT gene, mutations of the IDH1 or IDH2 gene, and mutations of FUBP1 (on 1p) or CIC (on 19q), have greatly enhanced our understanding of oligodendroglioma biology, although their diagnostic, prognostic, and predictive roles are less clear. […] It has therefore been suggested that complete 1p/19q codeletion be required for the diagnosis of canonical oligodendroglioma. […] This transition to an integrated morphological and molecular diagnosis may result in the disappearance of oligoastrocytoma as an entity, but brings new challenges as well. […] For instance it needs to be sorted out how (histopathological) criteria for grading of canonical oligodendrogliomas should be adapted, how pediatric oligodendrogliomas (known to lack codeletions) should be defined, which platforms and cut-off levels should ideally be used for demonstration of particular molecular aberrations, and how the diagnosis of oligodendroglioma should be made in centers/countries where molecular diagnostics is not available. […] Meanwhile, smart integration of morphological and molecular information will lead to recognition of biologically much more uniform groups within the spectrum of diffuse gliomas and thereby facilitate tailored treatments for individual patients.

• #70

  https://link.springer.com/article/10.1007/s00401-015-1424-1

  Through an altered substrate specificity, IDH mutations give rise to metabolic alterations, including an increase in production of 2-hydroxyglutarate (2-HG) which can inhibit histone demethylation and induces a glioma hypermethylation phenotype (glioma CpG island methylated phenotype or G-CIMP). […] In turn, this leads to a variety of downstream chromatin remodeling and transcriptional alterations. […] The presence of an IDH mutation may provide an opportunity to apply specific, IDH targeted treatment, no matter if the diagnosis was astrocytoma or (1p/19q codeleted) oligodendroglioma. […] This integrated diagnostic approach allows for much more robust recognition of biologically different subgroups within the spectrum of diffuse gliomas, thereby facilitating tailored treatment for individual patients.

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